rs762592772
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_000553.6(WRN):āc.3559A>Gā(p.Met1187Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000868 in 1,612,302 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. M1187I) has been classified as Uncertain significance.
Frequency
Consequence
NM_000553.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
WRN | NM_000553.6 | c.3559A>G | p.Met1187Val | missense_variant | 30/35 | ENST00000298139.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
WRN | ENST00000298139.7 | c.3559A>G | p.Met1187Val | missense_variant | 30/35 | 1 | NM_000553.6 | P1 | |
WRN | ENST00000521620.5 | n.2192A>G | non_coding_transcript_exon_variant | 18/23 | 1 | ||||
WRN | ENST00000650667.1 | c.*3173A>G | 3_prime_UTR_variant, NMD_transcript_variant | 29/34 |
Frequencies
GnomAD3 genomes ? AF: 0.0000133 AC: 2AN: 150734Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000795 AC: 2AN: 251440Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135892
GnomAD4 exome AF: 0.00000821 AC: 12AN: 1461568Hom.: 0 Cov.: 31 AF XY: 0.00000825 AC XY: 6AN XY: 727086
GnomAD4 genome ? AF: 0.0000133 AC: 2AN: 150734Hom.: 0 Cov.: 32 AF XY: 0.0000136 AC XY: 1AN XY: 73430
ClinVar
Submissions by phenotype
Werner syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 23, 2022 | This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1187 of the WRN protein (p.Met1187Val). This variant is present in population databases (rs762592772, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with WRN-related conditions. ClinVar contains an entry for this variant (Variation ID: 238159). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Not Available"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Not Available"). 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