rs121908447

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000298139.7(WRN):​c.3493C>A​(p.Gln1165Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q1165P) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

WRN
ENST00000298139.7 missense

Scores

1
5
13

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.19
Variant links:
Genes affected
WRN (HGNC:12791): (WRN RecQ like helicase) This gene encodes a member of the RecQ subfamily of DNA helicase proteins. The encoded nuclear protein is important in the maintenance of genome stability and plays a role in DNA repair, replication, transcription and telomere maintenance. This protein contains a N-terminal 3' to 5' exonuclease domain, an ATP-dependent helicase domain and RQC (RecQ helicase conserved region) domain in its central region, and a C-terminal HRDC (helicase RNase D C-terminal) domain and nuclear localization signal. Defects in this gene are the cause of Werner syndrome, an autosomal recessive disorder characterized by accelerated aging and an elevated risk for certain cancers. [provided by RefSeq, Aug 2017]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
WRNNM_000553.6 linkuse as main transcriptc.3493C>A p.Gln1165Lys missense_variant 30/35 ENST00000298139.7 NP_000544.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
WRNENST00000298139.7 linkuse as main transcriptc.3493C>A p.Gln1165Lys missense_variant 30/351 NM_000553.6 ENSP00000298139 P1
WRNENST00000521620.5 linkuse as main transcriptn.2126C>A non_coding_transcript_exon_variant 18/231
WRNENST00000650667.1 linkuse as main transcriptc.*3107C>A 3_prime_UTR_variant, NMD_transcript_variant 29/34 ENSP00000498593

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.17
BayesDel_addAF
Benign
-0.066
T
BayesDel_noAF
Benign
-0.33
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Benign
0.18
T
Eigen
Uncertain
0.34
Eigen_PC
Uncertain
0.45
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.90
D
M_CAP
Benign
0.020
T
MetaRNN
Uncertain
0.54
D
MetaSVM
Benign
-0.94
T
MutationAssessor
Benign
0.20
N
MutationTaster
Benign
1.0
D
PrimateAI
Benign
0.43
T
PROVEAN
Benign
-2.1
N
REVEL
Benign
0.18
Sift
Benign
0.070
T
Sift4G
Benign
0.12
T
Polyphen
0.96
D
Vest4
0.49
MutPred
0.54
Gain of catalytic residue at Q1165 (P = 0.0244);
MVP
0.75
MPC
0.44
ClinPred
0.96
D
GERP RS
5.2
Varity_R
0.75
gMVP
0.61

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-31004913; API