rs201384942
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_000553.6(WRN):āc.2108C>Gā(p.Thr703Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000434 in 1,613,922 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T703I) 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 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
WRN | NM_000553.6 | c.2108C>G | p.Thr703Ser | missense_variant | 19/35 | ENST00000298139.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
WRN | ENST00000298139.7 | c.2108C>G | p.Thr703Ser | missense_variant | 19/35 | 1 | NM_000553.6 | P1 | |
WRN | ENST00000521620.5 | n.741C>G | non_coding_transcript_exon_variant | 7/23 | 1 | ||||
WRN | ENST00000650667.1 | c.*1722C>G | 3_prime_UTR_variant, NMD_transcript_variant | 18/34 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152204Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000796 AC: 20AN: 251388Hom.: 0 AF XY: 0.0000810 AC XY: 11AN XY: 135868
GnomAD4 exome AF: 0.0000438 AC: 64AN: 1461718Hom.: 0 Cov.: 31 AF XY: 0.0000495 AC XY: 36AN XY: 727156
GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152204Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74368
ClinVar
Submissions by phenotype
Werner syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 24, 2022 | This sequence change replaces threonine, which is neutral and polar, with serine, which is neutral and polar, at codon 703 of the WRN protein (p.Thr703Ser). This variant is present in population databases (rs201384942, gnomAD 0.02%). 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: 528098). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Not Available". The serine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. RNA analysis performed to evaluate the impact of this missense change on mRNA splicing indicates it does not significantly alter splicing (Invitae). 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