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

Variant summary

Our verdict is Benign. The variant received -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

Publications

37 publications found

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 Gene-Disease associations (from GenCC):

autism spectrum disorder
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

XRCC6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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

GnomAD2 exomes

AF:

0.290

AC:

72679

AN:

250882

AF XY:

0.297

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 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

African (AFR)

AF:

0.0721

AC:

2412

AN:

33468

American (AMR)

AF:

0.183

AC:

8182

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.284

AC:

7425

AN:

26130

East Asian (EAS)

AF:

0.249

AC:

9887

AN:

39700

South Asian (SAS)

AF:

0.253

AC:

21832

AN:

86244

European-Finnish (FIN)

AF:

0.335

AC:

17879

AN:

53412

Middle Eastern (MID)

AF:

0.311

AC:

1747

AN:

5626

European-Non Finnish (NFE)

AF:

0.361

AC:

401891

AN:

1111792

Other (OTH)

AF:

0.323

AC:

19475

AN:

60344

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

20069

40138

60208

80277

100346

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12586

25172

37758

50344

62930

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.261

AC:

39678

AN:

152158

Hom.:

6315

Cov.:

AF XY:

0.258

AC XY:

19228

AN XY:

74384

show subpopulations

African (AFR)

AF:

0.0838

AC:

3482

AN:

41550

American (AMR)

AF:

0.242

AC:

3704

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.278

AC:

965

AN:

3468

East Asian (EAS)

AF:

0.246

AC:

1269

AN:

5168

South Asian (SAS)

AF:

0.243

AC:

1175

AN:

4828

European-Finnish (FIN)

AF:

0.339

AC:

3592

AN:

10582

Middle Eastern (MID)

AF:

0.293

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.360

AC:

24500

AN:

67966

Other (OTH)

AF:

0.303

AC:

638

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

1372

2745

4117

5490

6862

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

412

824

1236

1648

2060

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

(source)

DANN

Benign

0.86

PhyloP100

-1.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over