rs369277330
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP6
The NM_000553.6(WRN):c.968C>T(p.Ser323Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000229 in 1,613,780 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S323T) has been classified as Uncertain significance.
Frequency
Consequence
NM_000553.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
WRN | NM_000553.6 | c.968C>T | p.Ser323Leu | missense_variant | 9/35 | ENST00000298139.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
WRN | ENST00000298139.7 | c.968C>T | p.Ser323Leu | missense_variant | 9/35 | 1 | NM_000553.6 | P1 | |
WRN | ENST00000651642.1 | c.263C>T | p.Ser88Leu | missense_variant | 3/4 | ||||
WRN | ENST00000650667.1 | c.*582C>T | 3_prime_UTR_variant, NMD_transcript_variant | 8/34 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 152056Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251268Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135814
GnomAD4 exome AF: 0.0000246 AC: 36AN: 1461724Hom.: 0 Cov.: 32 AF XY: 0.0000179 AC XY: 13AN XY: 727166
GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 152056Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74278
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jun 14, 2022 | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 24728327) - |
Werner syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 24, 2024 | - - |
not specified Other:1
not provided, no classification provided | reference population | ITMI | Sep 19, 2013 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at