rs193302903
Variant summary
Our verdict is Pathogenic. Variant got 16 ACMG points: 16P and 0B. PM1PM2PM5PP3_ModeratePP5_Very_Strong
The ENST00000330775.9(SLC37A4):c.899G>A(p.Arg300His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000069 in 1,448,560 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. R300C) has been classified as Likely pathogenic.
Frequency
Consequence
ENST00000330775.9 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
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.899G>A | p.Arg300His | missense_variant | 9/11 | ENST00000642844.3 | |
SLC37A4 | NM_001164279.2 | c.680G>A | p.Arg227His | missense_variant | 9/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC37A4 | ENST00000330775.9 | c.899G>A | p.Arg300His | missense_variant | 8/10 | 5 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 6.90e-7 AC: 1AN: 1448560Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 719296
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Glucose-6-phosphate transport defect Pathogenic:3
Pathogenic, criteria provided, single submitter | clinical testing | Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center | Jul 05, 2023 | PS3, PM2, PM3, PM5 - |
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Jan 28, 2024 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Dec 02, 2023 | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 300 of the SLC37A4 protein (p.Arg300His). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with autosomal recessive SLC37A4-related conditions (PMID: 9781688, 15906092). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 68294). 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 with a positive predictive value of 80%. Experimental studies have shown that this missense change affects SLC37A4 function (PMID: 10940311, 12444104). For these reasons, this variant has been classified as Pathogenic. - |
not provided Pathogenic:1Other:1
not provided, no classification provided | literature only | UniProtKB/Swiss-Prot | - | - - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Mendelics | May 28, 2019 | - - |
Glycogen storage disease type 1 due to SLC37A4 mutation Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | DASA | Jan 05, 2022 | The c.899G>A;p.(Arg300His) missense variant has been observed in affected individual(s) and ClinVar contains an entry for this variant (Clinvar ID:68294; PMID: 15906092; 9781688) - PS4_moderateWell-established in vitro or in vivo functional studies support a damaging effect on the gene or gene product (PMID: 12444104; 10940311) - PS3_supporting. This variant is not present in population databases (rs193302903, gnomAD; ABraOM no frequency - http://abraom.ib.usp.br/) - PM2. The p.(Arg300His) was detected in trans with a pathogenic variant (PMID: 15906092; 9781688) - PM3_strong. Pathogenic missense variant in this residue have been reported (ClinVar ID: 68293) - PM5. In summary, the currently available evidence indicates that the variant is pathogenic. - |
Glucose-6-phosphate transport defect;C0342749:Phosphate transport defect;C5561986:Congenital disorder of glycosylation, type IIw Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Mar 02, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at