8-31088941-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_000553.6(WRN):c.1628A>G(p.Tyr543Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,459,230 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar 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
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
WRN | ENST00000298139.7 | c.1628A>G | p.Tyr543Cys | missense_variant | Exon 13 of 35 | 1 | NM_000553.6 | ENSP00000298139.5 | ||
WRN | ENST00000521620.5 | n.329A>G | non_coding_transcript_exon_variant | Exon 2 of 23 | 1 | |||||
WRN | ENST00000650667.1 | n.*1242A>G | non_coding_transcript_exon_variant | Exon 12 of 34 | ENSP00000498593.1 | |||||
WRN | ENST00000650667.1 | n.*1242A>G | 3_prime_UTR_variant | Exon 12 of 34 | ENSP00000498593.1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1459230Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 725836
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Werner syndrome Uncertain:1
This sequence change replaces tyrosine with cysteine at codon 543 of the WRN protein (p.Tyr543Cys). The tyrosine residue is moderately conserved and there is a large physicochemical difference between tyrosine and cysteine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with WRN-related conditions. 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: "Probably 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