11-119029287-C-T
Variant summary
Our verdict is Pathogenic. Variant got 16 ACMG points: 16P and 0B. PM1PM2PM5PP3_ModeratePP5_Very_Strong
The ENST00000330775.9(SLC37A4):c.83G>A(p.Arg28His) variant causes a missense change. The variant allele was found at a frequency of 0.0000109 in 1,461,468 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R28C) has been classified as Pathogenic.
Frequency
Consequence
ENST00000330775.9 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 16 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC37A4 | NM_001164277.2 | c.83G>A | p.Arg28His | missense_variant | 3/11 | ENST00000642844.3 | |
SLC37A4 | NM_001164279.2 | c.-172+105G>A | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC37A4 | ENST00000330775.9 | c.83G>A | p.Arg28His | missense_variant | 2/10 | 5 | P1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.0000121 AC: 3AN: 248886Hom.: 0 AF XY: 0.0000222 AC XY: 3AN XY: 135042
GnomAD4 exome AF: 0.0000109 AC: 16AN: 1461468Hom.: 0 Cov.: 31 AF XY: 0.0000124 AC XY: 9AN XY: 726994
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Glucose-6-phosphate transport defect Pathogenic:5
Pathogenic, no assertion criteria provided | literature only | OMIM | Feb 26, 1999 | - - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Counsyl | Aug 18, 2017 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Sep 22, 2023 | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 28 of the SLC37A4 protein (p.Arg28His). This variant is present in population databases (rs121908978, gnomAD 0.007%). This missense change has been observed in individuals with autosomal recessive glycogen storage disease (PMID: 10026167, 27066451, 28224773). ClinVar contains an entry for this variant (Variation ID: 6933). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt SLC37A4 protein function. Experimental studies have shown that this missense change affects SLC37A4 function (PMID: 10026167, 12444104, 18337460, 18835800). This variant disrupts the p.Arg28 amino acid residue in SLC37A4. Other variant(s) that disrupt this residue have been observed in individuals with SLC37A4-related conditions (PMID: 10026167, 10518030, 27066451, 28224773), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic. - |
Pathogenic, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Mar 25, 2024 | - - |
not provided Pathogenic:1Other:1
not provided, no classification provided | literature only | UniProtKB/Swiss-Prot | - | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Feb 26, 2022 | - - |
Glucose-6-phosphate transport defect;C0342749:Phosphate transport defect;C5561986:Congenital disorder of glycosylation, type IIw Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Nov 10, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at