rs796053253
Variant summary
Our verdict is Pathogenic. Variant got 16 ACMG points: 16P and 0B. PM1PM2PM5PP2PP3PP5_Very_Strong
The NM_006516.4(SLC2A1):c.971C>T(p.Ser324Leu) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,356 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 15/23 in silico tools predict a damaging outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. 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. S324P) has been classified as Pathogenic.
Frequency
Consequence
NM_006516.4 missense, splice_region
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 |
---|---|---|---|---|---|---|---|
SLC2A1 | NM_006516.4 | c.971C>T | p.Ser324Leu | missense_variant, splice_region_variant | 7/10 | ENST00000426263.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC2A1 | ENST00000426263.10 | c.971C>T | p.Ser324Leu | missense_variant, splice_region_variant | 7/10 | 1 | NM_006516.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1460356Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 726580
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Encephalopathy due to GLUT1 deficiency Pathogenic:2
Likely pathogenic, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Apr 11, 2023 | - - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Institute of Human Genetics, University of Leipzig Medical Center | Nov 18, 2021 | _x000D_ Criteria applied: PP1_STR, PS3_MOD, PS4_MOD, PM5, PM1_SUP, PM2_SUP, PP3 - |
GLUT1 deficiency syndrome 1, autosomal recessive Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jun 23, 2023 | This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with early-onset absence epilepsy and epilepsy and paroxysmal exercise-induced dyskinesia (PMID: 19798636, 20574033, 25099510). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 207201). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Experimental studies have shown that this missense change affects SLC2A1 function (PMID: 19798636). For these reasons, this variant has been classified as Pathogenic. This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 324 of the SLC2A1 protein (p.Ser324Leu). - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Jul 09, 2020 | Published functional studies demonstrate impaired glucose transport (Suls et al., 2009); Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 26986070, 20574033, 24847886, 19798636, 26633542, 21555602, 25487684, 25022942, 28717674, 29655203, 25099510) - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at