Submissions for variant NM_000155.4(GALT):c.820+13A>G

dbSNP: rs111033768

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000723491	SCV000331164	pathogenic	not provided	2017-07-03	criteria provided, single submitter	clinical testing
Mendelics	RCV000022211	SCV001137805	likely pathogenic	Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase	2019-05-28	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000022211	SCV001222162	pathogenic	Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase	2024-02-16	criteria provided, single submitter	clinical testing	This sequence change falls in intron 8 of the GALT gene. It does not directly change the encoded amino acid sequence of the GALT protein. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individuals with galactosemia (PMID: 23749220, 25052314). ClinVar contains an entry for this variant (Variation ID: 25269). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000022211	SCV002600456	pathogenic	Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase	2022-10-12	criteria provided, single submitter	clinical testing	Variant summary: GALT c.820+13A>G alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. Several computational tools predict a significant impact on normal splicing: Three predict the variant strengthens a cryptic intronic 5' splicing donor site. One predicts the variant creates a cryptic intronic 5' splicing donor site. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 251064 control chromosomes. c.820+13A>G has been reported in the literature as compound heterozygous and homozygous genotype in multiple individuals affected with and in a carrier of classic Galactosemia (example, Gort_2006, Coelho_2014, Papachristoforou_2019, Crespo_2020). These data indicate that the variant is very likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function (Coelho_2014, Crespo_2014). The most pronounced variant effect results in 0% of normal activity in a homozygous individual. Five clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Baylor Genetics	RCV000022211	SCV005058867	pathogenic	Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase	2024-02-15	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV000022211	SCV005675424	pathogenic	Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase	2024-01-19	criteria provided, single submitter	clinical testing
Counsyl	RCV000022211	SCV000486157	likely pathogenic	Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase	2016-04-07	no assertion criteria provided	clinical testing
Natera, Inc.	RCV001826500	SCV002085240	pathogenic	Galactosemia	2020-08-28	no assertion criteria provided	clinical testing