rs139323683
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_000553.6(WRN):c.3422C>T(p.Ser1141Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000492 in 1,613,848 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000553.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
WRN | NM_000553.6 | c.3422C>T | p.Ser1141Leu | missense_variant | 29/35 | ENST00000298139.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
WRN | ENST00000298139.7 | c.3422C>T | p.Ser1141Leu | missense_variant | 29/35 | 1 | NM_000553.6 | P1 | |
WRN | ENST00000521620.5 | n.2055C>T | non_coding_transcript_exon_variant | 17/23 | 1 | ||||
WRN | ENST00000650667.1 | c.*3036C>T | 3_prime_UTR_variant, NMD_transcript_variant | 28/34 |
Frequencies
GnomAD3 genomes ? AF: 0.000519 AC: 79AN: 152168Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.000859 AC: 216AN: 251384Hom.: 2 AF XY: 0.000839 AC XY: 114AN XY: 135864
GnomAD4 exome AF: 0.000489 AC: 715AN: 1461562Hom.: 2 Cov.: 31 AF XY: 0.000465 AC XY: 338AN XY: 727076
GnomAD4 genome ? AF: 0.000519 AC: 79AN: 152286Hom.: 1 Cov.: 32 AF XY: 0.000591 AC XY: 44AN XY: 74468
ClinVar
Submissions by phenotype
Werner syndrome Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
not specified Benign:1Other:1
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Oct 07, 2021 | - - |
not provided, no classification provided | reference population | ITMI | Sep 19, 2013 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Apr 22, 2016 | - - |
WRN-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 14, 2020 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at