rs3212024

Positions:

• chr14-103714398-G-A
• chr14-103714398-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005432.4(XRCC3):​c.-318+1026C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 151,420 control chromosomes in the GnomAD database, including 6,743 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 0.28 (6730 hom., cov: 29)
  • Exomes 𝑓: 0.34 (13 hom.)
• Consequence: XRCC3 NM_005432.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.896

Genes affected

XRCC3 (HGNC:12830): (X-ray repair cross complementing 3) This gene encodes a member of the RecA/Rad51-related protein family that participates in homologous recombination to maintain chromosome stability and repair DNA damage. This gene functionally complements Chinese hamster irs1SF, a repair-deficient mutant that exhibits hypersensitivity to a number of different DNA-damaging agents and is chromosomally unstable. A rare microsatellite polymorphism in this gene is associated with cancer in patients of varying radiosensitivity. Alternatively spliced transcript variants encoding the same protein have been identified. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.332 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XRCC3	NM_005432.4	c.-318+1026C>T		intron_variant		ENST00000555055.6	NP_005423.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XRCC3	ENST00000555055.6	c.-318+1026C>T		intron_variant		1	NM_005432.4	ENSP00000452598	P1

Frequencies

GnomAD3 genomes AF: 0.282 AC: 42572 AN: 151036 Hom.: 6719 Cov.: 29

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.309

Gnomad AMR AF: 0.289

Gnomad ASJ AF: 0.216

Gnomad EAS AF: 0.346

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.433

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.335

Gnomad OTH AF: 0.262

GnomAD4 exome AF: 0.340 AC: 91 AN: 268 Hom.: 13 AF XY: 0.333 AC XY: 64 AN XY: 192

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.125

Gnomad4 ASJ exome AF: 0.250

Gnomad4 EAS exome AF: 0.375

Gnomad4 SAS exome AF: 0.125

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.361

Gnomad4 OTH exome AF: 0.333

GnomAD4 genome AF: 0.282 AC: 42597 AN: 151152 Hom.: 6730 Cov.: 29 AF XY: 0.283 AC XY: 20872 AN XY: 73786

Gnomad4 AFR AF: 0.160

Gnomad4 AMR AF: 0.290

Gnomad4 ASJ AF: 0.216

Gnomad4 EAS AF: 0.346

Gnomad4 SAS AF: 0.200

Gnomad4 FIN AF: 0.433

Gnomad4 NFE AF: 0.335

Gnomad4 OTH AF: 0.263

Alfa AF: 0.312 Hom.: 1005

Bravo AF: 0.267

Asia WGS AF: 0.259 AC: 898 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.5
DANN	Benign	0.56

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

Other links and lift over

dbSNP: rs3212024; hg19: chr14-104180735;