rs773822420
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_000553.6(WRN):c.3897C>G(p.Cys1299Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. C1299C) has been classified as Likely benign.
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.3897C>G | p.Cys1299Trp | missense_variant | 33/35 | ENST00000298139.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
WRN | ENST00000298139.7 | c.3897C>G | p.Cys1299Trp | missense_variant | 33/35 | 1 | NM_000553.6 | P1 | |
WRN | ENST00000521620.5 | n.2530C>G | non_coding_transcript_exon_variant | 21/23 | 1 | ||||
WRN | ENST00000650667.1 | c.*3511C>G | 3_prime_UTR_variant, NMD_transcript_variant | 32/34 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome Cov.: 31
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Werner syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 28, 2021 | This variant is not present in population databases (ExAC no frequency). This sequence change replaces cysteine with tryptophan at codon 1299 of the WRN protein (p.Cys1299Trp). The cysteine residue is weakly conserved and there is a large physicochemical difference between cysteine and tryptophan. This variant has not been reported in the literature in individuals affected with WRN-related conditions. 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. 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"). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.