rs753161833
Variant summary
Our verdict is Pathogenic. Variant got 17 ACMG points: 17P and 0B. PM1PM2PM5PP2PP3_ModeratePP5_Very_Strong
The NM_006516.4(SLC2A1):āc.286A>Gā(p.Met96Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000138 in 1,448,662 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 (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M96T) has been classified as Likely pathogenic.
Frequency
Consequence
NM_006516.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 17 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC2A1 | NM_006516.4 | c.286A>G | p.Met96Val | missense_variant | 4/10 | ENST00000426263.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC2A1 | ENST00000426263.10 | c.286A>G | p.Met96Val | missense_variant | 4/10 | 1 | NM_006516.4 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.0000125 AC: 3AN: 240850Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 130918
GnomAD4 exome AF: 0.00000138 AC: 2AN: 1448662Hom.: 0 Cov.: 33 AF XY: 0.00000139 AC XY: 1AN XY: 721038
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Encephalopathy due to GLUT1 deficiency Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Apr 11, 2023 | - - |
not provided Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | May 01, 2021 | - - |
GLUT1 deficiency syndrome 1, autosomal recessive Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Aug 17, 2023 | This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 96 of the SLC2A1 protein (p.Met96Val). This variant is present in population databases (rs753161833, gnomAD 0.02%). This missense change has been observed in individual(s) with GLUT1-deficiency syndrome (PMID: 20129935, 26598494, 30588498). ClinVar contains an entry for this variant (Variation ID: 538680). 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 SLC2A1 protein function. Experimental studies have shown that this missense change affects SLC2A1 function (PMID: 30588498). For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at