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GeneBe

rs25489

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006297.3(XRCC1):c.839G>T(p.Arg280Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. 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. R280H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

XRCC1
NM_006297.3 missense

Scores

16

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.15
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 Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.105629295).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
XRCC1NM_006297.3 linkuse as main transcriptc.839G>T p.Arg280Leu missense_variant 9/17 ENST00000262887.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
XRCC1ENST00000262887.10 linkuse as main transcriptc.839G>T p.Arg280Leu missense_variant 9/171 NM_006297.3 P1

Frequencies

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

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.10
BayesDel_addAF
Benign
-0.18
T
BayesDel_noAF
Benign
-0.49
Cadd
Benign
14
Dann
Benign
0.77
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.20
N
M_CAP
Benign
0.0060
T
MetaRNN
Benign
0.11
T;T;T
MetaSVM
Benign
-0.97
T
MutationTaster
Benign
1.0
N;N
PrimateAI
Benign
0.41
T
PROVEAN
Benign
-2.0
N;N;.
REVEL
Benign
0.061
Sift
Benign
0.25
T;T;.
Sift4G
Benign
0.17
T;T;D
Polyphen
0.0010
.;B;.
Vest4
0.36
MutPred
0.36
Loss of methylation at R280 (P = 0.0206);.;.;
MVP
0.072
MPC
0.26
ClinPred
0.060
T
GERP RS
-0.70
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.6
gMVP
0.42

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs25489; hg19: chr19-44056412; API