8-31087857-A-G
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_000553.6(WRN):c.1513A>G(p.Thr505Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,196 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 Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
WRN | ENST00000298139.7 | c.1513A>G | p.Thr505Ala | missense_variant | Exon 12 of 35 | 1 | NM_000553.6 | ENSP00000298139.5 | ||
WRN | ENST00000521620.5 | n.214A>G | non_coding_transcript_exon_variant | Exon 1 of 23 | 1 | |||||
WRN | ENST00000650667.1 | n.*1127A>G | non_coding_transcript_exon_variant | Exon 11 of 34 | ENSP00000498593.1 | |||||
WRN | ENST00000650667.1 | n.*1127A>G | 3_prime_UTR_variant | Exon 11 of 34 | ENSP00000498593.1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152196Hom.: 0 Cov.: 32
GnomAD4 exome Cov.: 30
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152196Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74372
ClinVar
Submissions by phenotype
Werner syndrome Uncertain:1
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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The alanine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. This variant has not been reported in the literature in individuals affected with WRN-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 505 of the WRN protein (p.Thr505Ala). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at