rs200370409
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM2BP4_StrongBP6BS1
The NM_000553.6(WRN):c.3101A>T(p.Tyr1034Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000227 in 1,614,178 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 Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y1034H) has been classified as Uncertain significance.
Frequency
Consequence
NM_000553.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
WRN | NM_000553.6 | c.3101A>T | p.Tyr1034Phe | missense_variant | 25/35 | ENST00000298139.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
WRN | ENST00000298139.7 | c.3101A>T | p.Tyr1034Phe | missense_variant | 25/35 | 1 | NM_000553.6 | P1 | |
WRN | ENST00000521620.5 | n.1734A>T | non_coding_transcript_exon_variant | 13/23 | 1 | ||||
WRN | ENST00000650667.1 | c.*2715A>T | 3_prime_UTR_variant, NMD_transcript_variant | 24/34 |
Frequencies
GnomAD3 genomes ? AF: 0.000283 AC: 43AN: 152184Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000314 AC: 79AN: 251480Hom.: 0 AF XY: 0.000441 AC XY: 60AN XY: 135914
GnomAD4 exome AF: 0.000223 AC: 326AN: 1461876Hom.: 0 Cov.: 30 AF XY: 0.000298 AC XY: 217AN XY: 727240
GnomAD4 genome ? AF: 0.000269 AC: 41AN: 152302Hom.: 0 Cov.: 32 AF XY: 0.000201 AC XY: 15AN XY: 74468
ClinVar
Submissions by phenotype
WRN-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 13, 2024 | The WRN c.3101A>T variant is predicted to result in the amino acid substitution p.Tyr1034Phe. This variant was reported in an individual with dyskeratosis/aplastic anemia (Patient #48, Arias-Salgado et al. 2019. PubMed ID: 30995915). This variant was also documented in an individual with multiple types of cancer (Hodgkin lymphoma, lymphangioma, breast carcinoma); however, this individual also harbored chain-terminating variants in CDKN2A and PMS1 (http://www.oncm.org/v02p0088.htm). This variant is reported in 0.12% of alleles in individuals of South Asian descent in gnomAD and is interpreted as likely benign in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/238146/). Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Werner syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Wiskott-Aldrich syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | KCCC/NGS Laboratory, Kuwait Cancer Control Center | Jul 07, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at