chr2-233335029-C-G
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP3
The NM_000541.5(SAG):āc.874C>Gā(p.Arg292Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000483 in 1,613,874 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 Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R292Q) has been classified as Uncertain significance.
Frequency
Consequence
NM_000541.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SAG | NM_000541.5 | c.874C>G | p.Arg292Gly | missense_variant | 11/16 | ENST00000409110.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SAG | ENST00000409110.6 | c.874C>G | p.Arg292Gly | missense_variant | 11/16 | 5 | NM_000541.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152236Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000562 AC: 14AN: 249194Hom.: 0 AF XY: 0.0000592 AC XY: 8AN XY: 135188
GnomAD4 exome AF: 0.0000506 AC: 74AN: 1461638Hom.: 0 Cov.: 31 AF XY: 0.0000399 AC XY: 29AN XY: 727114
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152236Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74370
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 25, 2024 | This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 292 of the SAG protein (p.Arg292Gly). This variant is present in population databases (rs397514681, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with SAG-related conditions. ClinVar contains an entry for this variant (Variation ID: 967772). 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 not expected to disrupt SAG protein function with a negative predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at