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 (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y543C) 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.1628A>C | p.Tyr543Ser | missense_variant | 13/35 | ENST00000298139.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
WRN | ENST00000298139.7 | c.1628A>C | p.Tyr543Ser | missense_variant | 13/35 | 1 | NM_000553.6 | P1 | |
WRN | ENST00000521620.5 | n.329A>C | non_coding_transcript_exon_variant | 2/23 | 1 | ||||
WRN | ENST00000650667.1 | c.*1242A>C | 3_prime_UTR_variant, NMD_transcript_variant | 12/34 |
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
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 12, 2023 | 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). This variant is present in population databases (rs151001436, 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: 458388). 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. 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. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2022 | 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