rs138886038
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2
The NM_000553.6(WRN):c.3900C>A(p.Pro1300=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000674 in 1,613,952 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. P1300P) has been classified as Likely benign.
Frequency
Consequence
NM_000553.6 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -14 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
WRN | NM_000553.6 | c.3900C>A | p.Pro1300= | synonymous_variant | 33/35 | ENST00000298139.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
WRN | ENST00000298139.7 | c.3900C>A | p.Pro1300= | synonymous_variant | 33/35 | 1 | NM_000553.6 | P1 | |
WRN | ENST00000521620.5 | n.2533C>A | non_coding_transcript_exon_variant | 21/23 | 1 | ||||
WRN | ENST00000650667.1 | c.*3514C>A | 3_prime_UTR_variant, NMD_transcript_variant | 32/34 |
Frequencies
GnomAD3 genomes AF: 0.000848 AC: 129AN: 152070Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.000501 AC: 126AN: 251298Hom.: 1 AF XY: 0.000515 AC XY: 70AN XY: 135802
GnomAD4 exome AF: 0.000655 AC: 958AN: 1461882Hom.: 2 Cov.: 31 AF XY: 0.000661 AC XY: 481AN XY: 727242
GnomAD4 genome AF: 0.000848 AC: 129AN: 152070Hom.: 1 Cov.: 32 AF XY: 0.000862 AC XY: 64AN XY: 74270
ClinVar
Submissions by phenotype
not provided Benign:3
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, Amsterdam University Medical Center | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Feb 01, 2024 | WRN: BP4, BP7 - |
Werner syndrome Uncertain:1Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 16, 2024 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Feb 25, 2016 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at