rs374688634
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_000553.6(WRN):c.1879G>A(p.Val627Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000682 in 1,612,858 control chromosomes in the GnomAD database, with no homozygous occurrence. 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). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V627F) 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 -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
WRN | NM_000553.6 | c.1879G>A | p.Val627Ile | missense_variant | 16/35 | ENST00000298139.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
WRN | ENST00000298139.7 | c.1879G>A | p.Val627Ile | missense_variant | 16/35 | 1 | NM_000553.6 | P1 | |
WRN | ENST00000521620.5 | n.512G>A | non_coding_transcript_exon_variant | 4/23 | 1 | ||||
WRN | ENST00000650667.1 | c.*1493G>A | 3_prime_UTR_variant, NMD_transcript_variant | 15/34 |
Frequencies
GnomAD3 genomes ? AF: 0.0000395 AC: 6AN: 152054Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251084Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135690
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1460804Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2AN XY: 726682
GnomAD4 genome ? AF: 0.0000395 AC: 6AN: 152054Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74266
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jan 19, 2017 | - - |
Werner syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 19, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at