chr19-43546628-G-A

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5

The NM_006297.3(XRCC1):​c.1393C>T​(p.Gln465*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 32)

Consequence

XRCC1
NM_006297.3 stop_gained

Scores

3
2
2

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 3.04
Variant links:
Genes affected
XRCC1 (HGNC:12828): (X-ray repair cross complementing 1) The protein encoded by this gene is involved in the efficient repair of DNA single-strand breaks formed by exposure to ionizing radiation and alkylating agents. This protein interacts with DNA ligase III, polymerase beta and poly (ADP-ribose) polymerase to participate in the base excision repair pathway. It may play a role in DNA processing during meiogenesis and recombination in germ cells. A rare microsatellite polymorphism in this gene is associated with cancer in patients of varying radiosensitivity. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 11 ACMG points.

PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 19-43546628-G-A is Pathogenic according to our data. Variant chr19-43546628-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 433532.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
XRCC1NM_006297.3 linkc.1393C>T p.Gln465* stop_gained 12/17 ENST00000262887.10 NP_006288.2 P18887B2RCY5Q59HH7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
XRCC1ENST00000262887.10 linkc.1393C>T p.Gln465* stop_gained 12/171 NM_006297.3 ENSP00000262887.5 P18887
XRCC1ENST00000543982.5 linkc.1300C>T p.Gln434* stop_gained 11/162 ENSP00000443671.1 F5H8D7

Frequencies

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

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Spinocerebellar ataxia, autosomal recessive 26 Pathogenic:1
Pathogenic, no assertion criteria providedliterature onlyOMIMAug 22, 2017- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.55
D
BayesDel_noAF
Pathogenic
0.55
CADD
Pathogenic
38
DANN
Uncertain
1.0
Eigen
Pathogenic
0.70
Eigen_PC
Uncertain
0.50
FATHMM_MKL
Benign
0.65
D
Vest4
0.90
GERP RS
3.7

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1555768154; hg19: chr19-44050780; API