rs201036248
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM1BP4_StrongBP6BS2
The ENST00000330775.9(SLC37A4):c.467C>T(p.Ala156Val) variant causes a missense change. The variant allele was found at a frequency of 0.00237 in 1,611,414 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. 8/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. A156A) has been classified as Likely benign.
Frequency
Consequence
ENST00000330775.9 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC37A4 | NM_001164277.2 | c.467C>T | p.Ala156Val | missense_variant | 5/11 | ENST00000642844.3 | |
SLC37A4 | NM_001164279.2 | c.248C>T | p.Ala83Val | missense_variant | 5/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC37A4 | ENST00000330775.9 | c.467C>T | p.Ala156Val | missense_variant | 4/10 | 5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00205 AC: 312AN: 152244Hom.: 1 Cov.: 33
GnomAD3 exomes AF: 0.00166 AC: 403AN: 243018Hom.: 2 AF XY: 0.00163 AC XY: 215AN XY: 131964
GnomAD4 exome AF: 0.00241 AC: 3514AN: 1459052Hom.: 9 Cov.: 34 AF XY: 0.00240 AC XY: 1744AN XY: 725606
GnomAD4 genome ? AF: 0.00205 AC: 312AN: 152362Hom.: 1 Cov.: 33 AF XY: 0.00209 AC XY: 156AN XY: 74504
ClinVar
Submissions by phenotype
Glucose-6-phosphate transport defect Benign:2
Likely benign, no assertion criteria provided | clinical testing | Natera, Inc. | Apr 03, 2020 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 13, 2020 | This variant is associated with the following publications: (PMID: 22899091) - |
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2023 | SLC37A4: BP4, BS1, BS2 - |
Glycogen storage disease, type I Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | 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. - |
Glucose-6-phosphate transport defect;C0342749:Phosphate transport defect Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago | Oct 01, 2021 | 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. - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Aug 02, 2023 | 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at