rs25489

chr19-43552260-C-Achr19-43552260-C-Gchr19-43552260-C-T

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PM2_SupportingBP4_Moderate

The NM_006297(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 Genomes 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 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.15

Links

XRCC1 (HGNC:12828):

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

PM2

Very rare variant; Number of alleles below threshold, Median coverage is 32.

BP4

Computational evidence support a benign effect (MetaRNN=0.105629295).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XRCC1	NM_006297.3 linkuse as main transcript	c.839G>T	p.Arg280Leu	missense_variant	9/17	ENST00000262887.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XRCC1	ENST00000262887.10 linkuse as main transcript	c.839G>T	p.Arg280Leu	missense_variant	9/17	1	NM_006297.3	P1

Frequencies

GnomAD3 genomes

Cov.:

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

BayesDel_noAF

Benign

-0.49

Cadd

Benign

Dann

Benign

0.77

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.20

M_CAP

Benign

0.0060

MetaRNN

Benign

0.11

T;T;T

MetaSVM

Benign

-0.97

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.41

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

GERP RS

-0.70

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

gMVP

0.42

Splicing

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

Publications

LitVar

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Links

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over