rs587777209
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PP5_Moderate
The NM_000541.5(SAG):c.523C>T(p.Arg175Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000992 in 1,613,022 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 Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. R175R) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_000541.5 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SAG | NM_000541.5 | c.523C>T | p.Arg175Ter | stop_gained | 8/16 | ENST00000409110.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SAG | ENST00000409110.6 | c.523C>T | p.Arg175Ter | stop_gained | 8/16 | 5 | NM_000541.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152200Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000805 AC: 2AN: 248498Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 134826
GnomAD4 exome AF: 0.0000103 AC: 15AN: 1460822Hom.: 0 Cov.: 31 AF XY: 0.0000151 AC XY: 11AN XY: 726660
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152200Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74364
ClinVar
Submissions by phenotype
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Feb 13, 2022 | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 102422). This premature translational stop signal has been observed in individual(s) with Oguchi disease (PMID: 15234147). This variant is present in population databases (rs587777209, gnomAD 0.003%). This sequence change creates a premature translational stop signal (p.Arg175*) in the SAG gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SAG are known to be pathogenic (PMID: 9452120, 15234147, 22665972). - |
Oguchi disease Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jul 01, 2004 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at