rs151001436
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_000553.6(WRN):c.1628A>C(p.Tyr543Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000248 in 1,611,324 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>C | p.Tyr543Ser | missense_variant | Exon 13 of 35 | 1 | NM_000553.6 | ENSP00000298139.5 | ||
WRN | ENST00000521620.5 | n.329A>C | non_coding_transcript_exon_variant | Exon 2 of 23 | 1 | |||||
WRN | ENST00000650667.1 | n.*1242A>C | non_coding_transcript_exon_variant | Exon 12 of 34 | ENSP00000498593.1 | |||||
WRN | ENST00000650667.1 | n.*1242A>C | 3_prime_UTR_variant | Exon 12 of 34 | ENSP00000498593.1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152094Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 249076Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 134578
GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1459230Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 725836
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152094Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74282
ClinVar
Submissions by phenotype
Werner syndrome Uncertain:1
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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 458388). This variant has not been reported in the literature in individuals affected with WRN-related conditions. This variant is present in population databases (rs151001436, gnomAD 0.007%). This sequence change replaces tyrosine, which is neutral and polar, with serine, which is neutral and polar, at codon 543 of the WRN protein (p.Tyr543Ser). -
not provided Uncertain:1
In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at