Submissions for variant NM_001164277.2(SLC37A4):c.467C>T (p.Ala156Val)

gnomAD frequency: 0.00214  dbSNP: rs201036248

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000658627	SCV000252288	likely benign	not provided	2020-04-13	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 22899091)
Labcorp Genetics (formerly Invitae), Labcorp	RCV001086520	SCV000755872	benign	Glucose-6-phosphate transport defect	2024-01-31	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000658627	SCV000780409	benign	not provided	2023-07-01	criteria provided, single submitter	clinical testing	SLC37A4: BP4, BS1, BS2
Illumina Laboratory Services, Illumina	RCV001102581	SCV001259266	uncertain significance	Glycogen storage disease, type I	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV002054342	SCV002495964	uncertain significance	Phosphate transport defect; Glucose-6-phosphate transport defect	2021-10-01	criteria provided, single submitter	clinical testing	SLC37A4 NM_001164277.1 exon 4 p.Ala156Val (c.467C>T): This variant has been reported in the literature in 1 individual with features suggestive of a glycogen storage disease; of note, it was one of three SLC37A4 variants identified in this individual, determined to be in cis with one variant and of unknown phase with the other (Wang 2013 PMID:22899091). This variant is present in 0.4% (42/10624) of Finnish alleles and in 1 homozygote in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/11-119027787-G-A?dataset=gnomad_r3). This variant is present in ClinVar (Variation ID:215177). Evolutionary conservation and computational predictive tools for this variant are unclear. Splice prediction tools suggest that this variant may affect splicing. However, further studies are needed to understand its impact. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003330569	SCV004037986	benign	not specified	2023-08-02	criteria provided, single submitter	clinical testing	Variant summary: SLC37A4 c.467C>T (p.Ala156Val) results in a non-conservative amino acid change located in the Major facilitator superfamily domain (IPR020846) of the encoded protein sequence. One of two in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0019 in 274424 control chromosomes, including 2 homozygotes (gnomAD). The variant was found predominantly at a frequency of 0.003 within the Non-Finnish European subpopulation in the gnomAD database. The observed variant frequency within Non-Finnish European control individuals in the gnomAD database is approximately 2.5 fold of the estimated maximal expected allele frequency for a pathogenic variant in SLC37A4 causing Glycogen Storage Disease Type Ib (0.0012), strongly suggesting that the variant is a benign polymorphism found primarily in populations of Non-Finnish European origin. c.467C>T has been reported in the literature occuring in cis with variant c.572C>T [p.Pro191Arg] in one individual affected with Glycogen Storage Disease Type Ib (Wang_2013). This report does not provide unequivocal conclusions about association of the variant with Glycogen Storage Disease Type Ib. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 22899091). Six ClinVar submitters have assessed the variant since 2014: three classified the variant as uncertain significance, two as likely benign, and one as benign. Based on the evidence outlined above, the variant was classified as benign.
Natera, Inc.	RCV001086520	SCV001466218	likely benign	Glucose-6-phosphate transport defect	2020-04-03	no assertion criteria provided	clinical testing