rs200403732
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_000553.6(WRN):c.4001T>G(p.Leu1334Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000316 in 1,613,040 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 Uncertain significance (★★).
Frequency
Consequence
NM_000553.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
WRN | NM_000553.6 | c.4001T>G | p.Leu1334Arg | missense_variant | 34/35 | ENST00000298139.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
WRN | ENST00000298139.7 | c.4001T>G | p.Leu1334Arg | missense_variant | 34/35 | 1 | NM_000553.6 | P1 | |
ENST00000521252.1 | downstream_gene_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152138Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000279 AC: 7AN: 250740Hom.: 0 AF XY: 0.0000369 AC XY: 5AN XY: 135542
GnomAD4 exome AF: 0.0000308 AC: 45AN: 1460784Hom.: 0 Cov.: 30 AF XY: 0.0000206 AC XY: 15AN XY: 726678
GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152256Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74456
ClinVar
Submissions by phenotype
Werner syndrome Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 03, 2022 | This sequence change replaces leucine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 1334 of the WRN protein (p.Leu1334Arg). This variant is present in population databases (rs200403732, gnomAD 0.005%). 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: 458475). 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: "Benign"; 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 | Fulgent Genetics, Fulgent Genetics | Feb 24, 2022 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden | Nov 03, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at