Submissions for variant NM_000155.4(GALT):c.940A>G (p.Asn314Asp)

gnomAD frequency: 0.07150  dbSNP: rs2070074

Total submissions: 21

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000078243	SCV000110081	other	not provided	2018-02-13	criteria provided, single submitter	clinical testing
GeneDx	RCV000078243	SCV000238875	benign	not provided	2021-07-15	criteria provided, single submitter	clinical testing	Observed on 25366/282804 (9%) alleles including multiple unrelated homozygous individuals in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 2011574, 25592817, 9222760, 27005423, 8892021, 19581158, 21228398, 11152465, 22963887, 25614870, 8198125, 15841485, 25087612, 16540753, 31028937, 31194252, 19224951)
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000078243	SCV000281474	pathogenic	not provided	2014-11-18	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000309989	SCV000479769	likely benign	Galactosemia	2016-06-14	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000022233	SCV000603779	benign	Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase	2023-11-29	criteria provided, single submitter	clinical testing
Counsyl	RCV000022233	SCV000800785	benign	Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase	2017-09-11	criteria provided, single submitter	clinical testing
Mendelics	RCV000022233	SCV001137809	benign	Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase	2019-05-28	criteria provided, single submitter	clinical testing
UNC Molecular Genetics Laboratory, University of North Carolina at Chapel Hill	RCV000022233	SCV001251539	likely pathogenic	Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase		criteria provided, single submitter	research	Four variants in the GALT gene often occur together on the same chromosome (in cis) as part of a haplotype, which is referred to as the Duarte 2 variant: (c.378-27G>C, c.507+62G>A, c.508-24G>A, c.940A>G). Individuals that inherit the Duarte 2 variant from one parent and a more severe GALT variant from the other parent are affected with Duarte galactosemia, and typically have milder features of galactosemia (PMID: 25473725; 24718839; 19224951; 10424825).
Labcorp Genetics (formerly Invitae), Labcorp	RCV000022233	SCV001720274	benign	Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase	2024-02-01	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000022233	SCV001737351	likely benign	Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase	2021-06-10	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000022233	SCV003835280	pathogenic	Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase	2023-11-10	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000078243	SCV004010829	likely benign	not provided	2024-08-01	criteria provided, single submitter	clinical testing	GALT: BP4
Mayo Clinic Laboratories, Mayo Clinic	RCV000078243	SCV005046903	pathogenic	not provided	2022-06-24	criteria provided, single submitter	clinical testing
Neuberg Centre For Genomic Medicine, NCGM	RCV000022233	SCV005374759	likely pathogenic	Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase		criteria provided, single submitter	clinical testing	The missense variant c.940A>G (p.Asn314Asp) in the GALT gene has been reported previously in heterozygous and homozygous state in individuals affected with galactosemia. It is one of the most prevalent variants in the Indian population. This mutation effect may cause differences in the protein’s physiochemical characteristics that may be disturbed by either stabilizing or destabilizing the protein. Four variants in the GALT gene often occur together on the same chromosome (in cis) as part of a haplotype, which is referred to as the Duarte 2 variant: (c.378-27G>C, c.507+62G>A, c.508-24G>A, c.940A>G) (Kumar S et al., 2020; Klipstein et al., 2003; Lukac-Bajalo et al., 2002; Carney et al., 2009). This variant is reported with the allele frequency (9%) in the gnomAD Exomes. It is submitted to ClinVar with varying interpretations as Pathogenic/ Likely Pathogenic/ Benign/ Likely benign. The amino acid Asparagine at position 314 is changed to a Aspartic Acid changing protein sequence and it might alter its composition and physico-chemical properties. Multiple lines of computational evidence (Polyphen - Benign, SIFT - Tolerated and MutationTaster-Polymorphism) predict no damaging effect on protein structure and function for this variant. The amino acid change p.Asn314Asp in GALT is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Pathogenic. In the absence of another reportable variant, the molecular diagnosis is not confirmed.
OMIM	RCV000003797	SCV000023962	benign	GALT POLYMORPHISM (DUARTE, D2)	2009-05-01	no assertion criteria provided	literature only
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000022233	SCV000052477	benign	Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase	2015-10-06	no assertion criteria provided	clinical testing
GeneReviews	RCV000022233	SCV000257440	not provided	Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase		no assertion provided	literature only
PreventionGenetics, part of Exact Sciences	RCV003891427	SCV000302734	likely benign	GALT-related disorder	2019-06-21	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Division of Human Genetics, Children's Hospital of Philadelphia	RCV000022233	SCV000536727	pathogenic	Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase	2016-06-10	no assertion criteria provided	research
Lifecell International Pvt. Ltd	RCV000022233	SCV001478376	benign	Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase		no assertion criteria provided	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV000078243	SCV001552853	uncertain significance	not provided		no assertion criteria provided	clinical testing