Genetic Variant XRCC6:p.Gly593Gly (chr22-41663764-G-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_001469.5(XRCC6):c.1779G>T(p.Gly593Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.329 in 1,613,588 control chromosomes in the GnomAD database, including 91,680 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.26 ( 6315 hom., cov: 32)

Exomes 𝑓: 0.34 ( 85365 hom. )

Consequence

XRCC6
NM_001469.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.06

Variant links:

Genes affected

XRCC6 (HGNC:4055): (X-ray repair cross complementing 6) The p70/p80 autoantigen is a nuclear complex consisting of two subunits with molecular masses of approximately 70 and 80 kDa. The complex functions as a single-stranded DNA-dependent ATP-dependent helicase. The complex may be involved in the repair of nonhomologous DNA ends such as that required for double-strand break repair, transposition, and V(D)J recombination. High levels of autoantibodies to p70 and p80 have been found in some patients with systemic lupus erythematosus. [provided by RefSeq, Jul 2008]

XRCC6 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP7

Synonymous conserved (PhyloP=-1.06 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.357 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XRCC6	NM_001469.5 link	c.1779G>T	p.Gly593Gly	synonymous_variant	Exon 13 of 13	ENST00000360079.8	NP_001460.1	P12956-1A0A024R1N4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XRCC6	ENST00000360079.8 link	c.1779G>T	p.Gly593Gly	synonymous_variant	Exon 13 of 13	1	NM_001469.5	ENSP00000353192.3		P12956-1

Frequencies

GnomAD3 genomes

AF:

0.261

AC:

39673

AN:

152040

Hom.:

6307

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0840

Gnomad AMI

AF:

0.293

Gnomad AMR

AF:

0.243

Gnomad ASJ

AF:

0.278

Gnomad EAS

AF:

0.246

Gnomad SAS

AF:

0.244

Gnomad FIN

AF:

0.339

Gnomad MID

AF:

0.288

Gnomad NFE

AF:

0.360

Gnomad OTH

AF:

0.296

GnomAD3 exomes

AF:

0.290

AC:

72679

AN:

250882

Hom.:

11689

AF XY:

0.297

AC XY:

40356

AN XY:

135672

show subpopulations

Gnomad AFR exome

AF:

0.0774

Gnomad AMR exome

AF:

0.175

Gnomad ASJ exome

AF:

0.282

Gnomad EAS exome

AF:

0.248

Gnomad SAS exome

AF:

0.261

Gnomad FIN exome

AF:

0.339

Gnomad NFE exome

AF:

0.359

Gnomad OTH exome

AF:

0.316

GnomAD4 exome

AF:

0.336

AC:

490730

AN:

1461430

Hom.:

85365

Cov.:

AF XY:

0.334

AC XY:

242925

AN XY:

727042

show subpopulations

Gnomad4 AFR exome

AF:

0.0721

Gnomad4 AMR exome

AF:

0.183

Gnomad4 ASJ exome

AF:

0.284

Gnomad4 EAS exome

AF:

0.249

Gnomad4 SAS exome

AF:

0.253

Gnomad4 FIN exome

AF:

0.335

Gnomad4 NFE exome

AF:

0.361

Gnomad4 OTH exome

AF:

0.323

GnomAD4 genome

AF:

0.261

AC:

39678

AN:

152158

Hom.:

6315

Cov.:

AF XY:

0.258

AC XY:

19228

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.0838

Gnomad4 AMR

AF:

0.242

Gnomad4 ASJ

AF:

0.278

Gnomad4 EAS

AF:

0.246

Gnomad4 SAS

AF:

0.243

Gnomad4 FIN

AF:

0.339

Gnomad4 NFE

AF:

0.360

Gnomad4 OTH

AF:

0.303

Alfa

AF:

0.283

Hom.:

3047

Bravo

AF:

0.246

Asia WGS

AF:

0.297

AC:

1031

AN:

3478

EpiCase

AF:

0.352

EpiControl

AF:

0.364

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

5.1

DANN

Benign

0.86

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over