Variant chr19-43546079-G-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_006297.3(XRCC1):c.1454C>A(p.Ser485Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.000456 in 1,610,810 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.00042 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00046 ( 0 hom. )

Consequence

XRCC1
NM_006297.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 4.76

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]

XRCC1 links:

Genome browser will be placed here

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=0.11575717).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XRCC1	NM_006297.3 linkuse as main transcript	c.1454C>A	p.Ser485Tyr	missense_variant	13/17	ENST00000262887.10	NP_006288.2	P18887B2RCY5Q59HH7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XRCC1	ENST00000262887.10 linkuse as main transcript	c.1454C>A	p.Ser485Tyr	missense_variant	13/17	1	NM_006297.3	ENSP00000262887.5		P18887
XRCC1	ENST00000543982.5 linkuse as main transcript	c.1361C>A	p.Ser454Tyr	missense_variant	12/16	2		ENSP00000443671.1		F5H8D7

Frequencies

GnomAD3 genomes

AF:

0.000423

AC:

AN:

149034

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000995

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000400

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000743

Gnomad OTH

AF:

0.00148

GnomAD3 exomes

AF:

0.000302

AC:

AN:

251388

Hom.:

AF XY:

0.000309

AC XY:

AN XY:

135864

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.000434

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000466

Gnomad OTH exome

AF:

0.000652

GnomAD4 exome

AF:

0.000459

AC:

671

AN:

1461638

Hom.:

Cov.:

AF XY:

0.000459

AC XY:

334

AN XY:

727142

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.000380

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000564

Gnomad4 OTH exome

AF:

0.000398

GnomAD4 genome

AF:

0.000422

AC:

AN:

149172

Hom.:

Cov.:

AF XY:

0.000316

AC XY:

AN XY:

72886

show subpopulations

Gnomad4 AFR

AF:

0.0000992

Gnomad4 AMR

AF:

0.000400

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000743

Gnomad4 OTH

AF:

0.00146

Alfa

AF:

0.0304

Hom.:

2350

Bravo

AF:

0.000397

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.000930

AC:

ExAC

AF:

0.000214

AC:

EpiCase

AF:

0.000327

EpiControl

AF:

0.000474

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Uncertain:2

Uncertain significance, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Uncertain significance, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Dec 01, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.39

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.17

.;T

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.86

.;D

M_CAP

Benign

0.0098

MetaRNN

Benign

0.12

T;T

MetaSVM

Benign

-1.2

PrimateAI

Uncertain

0.50

PROVEAN

Uncertain

-3.1

D;D

REVEL

Benign

0.12

Sift

Benign

0.10

T;T

Sift4G

Uncertain

0.0030

D;D

Polyphen

0.98

.;D

Vest4

0.41

MVP

0.39

MPC

0.82

ClinPred

0.15

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

gMVP

0.28

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over