rs532588948
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_000553.6(WRN):āc.2947A>Gā(p.Ile983Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000576 in 1,614,106 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Consequence
NM_000553.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
WRN | NM_000553.6 | c.2947A>G | p.Ile983Val | missense_variant | 24/35 | ENST00000298139.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
WRN | ENST00000298139.7 | c.2947A>G | p.Ile983Val | missense_variant | 24/35 | 1 | NM_000553.6 | P1 | |
WRN | ENST00000521620.5 | n.1580A>G | non_coding_transcript_exon_variant | 12/23 | 1 | ||||
WRN | ENST00000650667.1 | c.*2561A>G | 3_prime_UTR_variant, NMD_transcript_variant | 23/34 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152164Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251280Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135818
GnomAD4 exome AF: 0.0000609 AC: 89AN: 1461824Hom.: 1 Cov.: 31 AF XY: 0.0000578 AC XY: 42AN XY: 727208
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152282Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74456
ClinVar
Submissions by phenotype
Werner syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 13, 2022 | This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 983 of the WRN protein (p.Ile983Val). This variant is present in population databases (rs532588948, gnomAD 0.007%). 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: 404052). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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