rs201282577
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_000553.6(WRN):āc.2300C>Gā(p.Thr767Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000613 in 1,613,804 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 (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T767A) 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.2300C>G | p.Thr767Arg | missense_variant | 20/35 | ENST00000298139.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
WRN | ENST00000298139.7 | c.2300C>G | p.Thr767Arg | missense_variant | 20/35 | 1 | NM_000553.6 | P1 | |
WRN | ENST00000521620.5 | n.933C>G | non_coding_transcript_exon_variant | 8/23 | 1 | ||||
WRN | ENST00000650667.1 | c.*1914C>G | 3_prime_UTR_variant, NMD_transcript_variant | 19/34 |
Frequencies
GnomAD3 genomes ? AF: 0.0000526 AC: 8AN: 152144Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000756 AC: 19AN: 251236Hom.: 0 AF XY: 0.0000810 AC XY: 11AN XY: 135780
GnomAD4 exome AF: 0.0000623 AC: 91AN: 1461660Hom.: 0 Cov.: 30 AF XY: 0.0000536 AC XY: 39AN XY: 727132
GnomAD4 genome ? AF: 0.0000526 AC: 8AN: 152144Hom.: 0 Cov.: 33 AF XY: 0.0000404 AC XY: 3AN XY: 74310
ClinVar
Submissions by phenotype
Werner syndrome Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 26, 2022 | This sequence change replaces threonine, which is neutral and polar, with arginine, which is basic and polar, at codon 767 of the WRN protein (p.Thr767Arg). This variant is present in population databases (rs201282577, gnomAD 0.05%). 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: 458415). 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Jun 07, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at