22-41629053-A-G

Variant names:

• chr22-41629053-A-G
• rs5751131
• NM_001469.5:c.195+823A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001469.5(XRCC6):​c.195+823A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0178 in 151,828 control chromosomes in the GnomAD database, including 610 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 0.018 (610 hom., cov: 31)
• Consequence: XRCC6 NM_001469.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.185
• Publications: 5 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.46 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001469.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XRCC6	NM_001469.5	MANE Select	c.195+823A>G		intron	N/A	NP_001460.1
	XRCC6	NM_001288976.2		c.195+823A>G		intron	N/A	NP_001275905.1
	XRCC6	NM_001288977.2		c.195+823A>G		intron	N/A	NP_001275906.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XRCC6	ENST00000360079.8	TSL:1 MANE Select	c.195+823A>G		intron	N/A	ENSP00000353192.3
	XRCC6	ENST00000359308.8	TSL:1	c.195+823A>G		intron	N/A	ENSP00000352257.4
	XRCC6	ENST00000405878.5	TSL:5	c.195+823A>G		intron	N/A	ENSP00000384257.1

Frequencies

GnomAD3 genomes AF: 0.0179 AC: 2717 AN: 151710 Hom.: 613 Cov.: 31

Gnomad AFR AF: 0.00184

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00376

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.476

Gnomad SAS AF: 0.0189

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.0158

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0178 AC: 2710 AN: 151828 Hom.: 610 Cov.: 31 AF XY: 0.0200 AC XY: 1484 AN XY: 74186

African (AFR) AF: 0.00183 AC: 76 AN: 41430

American (AMR) AF: 0.00375 AC: 57 AN: 15180

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.476 AC: 2441 AN: 5126

South Asian (SAS) AF: 0.0185 AC: 89 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10542

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000191 AC: 13 AN: 67958

Other (OTH) AF: 0.0161 AC: 34 AN: 2106

Alfa AF: 0.00344 Hom.: 115

Bravo AF: 0.0205

Asia WGS AF: 0.175 AC: 606 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	13
DANN	Benign	0.88
PhyloP100		0.18
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs5751131; hg19: chr22-42025057;