rs772108759
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_000553.6(WRN):c.350T>C(p.Met117Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000805 in 1,614,002 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 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. M117V) 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 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
WRN | NM_000553.6 | c.350T>C | p.Met117Thr | missense_variant | 4/35 | ENST00000298139.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
WRN | ENST00000298139.7 | c.350T>C | p.Met117Thr | missense_variant | 4/35 | 1 | NM_000553.6 | P1 | |
WRN | ENST00000650667.1 | c.210-486T>C | intron_variant, NMD_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152210Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251408Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135882
GnomAD4 exome AF: 0.00000684 AC: 10AN: 1461792Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3AN XY: 727200
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152210Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74372
ClinVar
Submissions by phenotype
Werner syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 09, 2022 | This sequence change replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 117 of the WRN protein (p.Met117Thr). This variant is present in population databases (rs772108759, gnomAD 0.0009%). 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: 404056). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Not Available"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Not Available"). 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at