rs16384

Variant names:

• chr22-41649005-A-AAAC
• rs16384
• NM_001469.5:c.961-1717_961-1716insACA

Your query was ambiguous. Multiple possible variants found:

• chr22-41649005-A-AAAC
• chr22-41649005-A-AAAT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001469.5(XRCC6):​c.961-1717_961-1716insACA variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.84 (53893 hom., cov: 0)
• Consequence: XRCC6 NM_001469.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.231
• Publications: 4 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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.945 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XRCC6	NM_001469.5	MANE Select	c.961-1717_961-1716insACA		intron	N/A	NP_001460.1	P12956-1
	XRCC6	NM_001288976.2		c.961-1717_961-1716insACA		intron	N/A	NP_001275905.1	P12956-1
	XRCC6	NM_001288977.2		c.838-1717_838-1716insACA		intron	N/A	NP_001275906.1	P12956-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XRCC6	ENST00000360079.8	TSL:1 MANE Select	c.961-1718_961-1717insAAC		intron	N/A	ENSP00000353192.3	P12956-1
	XRCC6	ENST00000359308.8	TSL:1	c.961-1718_961-1717insAAC		intron	N/A	ENSP00000352257.4	P12956-1
	XRCC6	ENST00000938034.1		c.961-1718_961-1717insAAC		intron	N/A	ENSP00000608093.1

Frequencies

GnomAD3 genomes AF: 0.838 AC: 126366 AN: 150788 Hom.: 53844 Cov.: 0

Gnomad AFR AF: 0.953

Gnomad AMI AF: 0.704

Gnomad AMR AF: 0.648

Gnomad ASJ AF: 0.715

Gnomad EAS AF: 0.942

Gnomad SAS AF: 0.706

Gnomad FIN AF: 0.809

Gnomad MID AF: 0.785

Gnomad NFE AF: 0.826

Gnomad OTH AF: 0.805

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

GnomAD4 genome AF: 0.838 AC: 126465 AN: 150898 Hom.: 53893 Cov.: 0 AF XY: 0.830 AC XY: 61124 AN XY: 73612

African (AFR) AF: 0.952 AC: 39212 AN: 41170

American (AMR) AF: 0.647 AC: 9684 AN: 14966

Ashkenazi Jewish (ASJ) AF: 0.715 AC: 2471 AN: 3456

East Asian (EAS) AF: 0.943 AC: 4856 AN: 5150

South Asian (SAS) AF: 0.705 AC: 3373 AN: 4784

European-Finnish (FIN) AF: 0.809 AC: 8333 AN: 10298

Middle Eastern (MID) AF: 0.800 AC: 232 AN: 290

European-Non Finnish (NFE) AF: 0.826 AC: 55985 AN: 67794

Other (OTH) AF: 0.807 AC: 1683 AN: 2086

Alfa AF: 0.784 Hom.: 2001

Bravo AF: 0.827

Asia WGS AF: 0.838 AC: 2911 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.23
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs16384;

hg19: chr22-42045009;