rs1057517822
Variant summary
Our verdict is Pathogenic. Variant got 14 ACMG points: 14P and 0B. PS1PM1PM2PM5PP2PP3PP5_Moderate
The NM_006516.4(SLC2A1):c.418G>C(p.Val140Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely pathogenicin ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V140M) has been classified as Pathogenic.
Frequency
Consequence
NM_006516.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 14 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SLC2A1 | NM_006516.4 | c.418G>C | p.Val140Leu | missense_variant | 4/10 | ENST00000426263.10 | NP_006507.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SLC2A1 | ENST00000426263.10 | c.418G>C | p.Val140Leu | missense_variant | 4/10 | 1 | NM_006516.4 | ENSP00000416293.2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 32
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
GLUT1 deficiency syndrome 1, autosomal recessive Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Feb 08, 2022 | For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Val140 amino acid residue in SLC2A1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 18577546, 29356177). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 140 of the SLC2A1 protein (p.Val140Leu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with SLC2A1-related conditions (PMID: 31273778; Invitae). ClinVar contains an entry for this variant (Variation ID: 538677). 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at