rs3212024

Variant names:

• chr14-103714398-G-A
• rs3212024
• NM_005432.4:c.-318+1026C>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

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

The ENST00000555055.6(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 ENST00000555055.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.896
• Publications: 9 publications found

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]

KLC1 (HGNC:6387): (kinesin light chain 1) Conventional kinesin is a tetrameric molecule composed of two heavy chains and two light chains, and transports various cargos along microtubules toward their plus ends. The heavy chains provide the motor activity, while the light chains bind to various cargos. This gene encodes a member of the kinesin light chain family. It associates with kinesin heavy chain through an N-terminal domain, and six tetratricopeptide repeat (TPR) motifs are thought to be involved in binding of cargos such as vesicles, mitochondria, and the Golgi complex. Thus, kinesin light chains function as adapter molecules and not motors per se. Although previously named "kinesin 2", this gene is not a member of the kinesin-2 / kinesin heavy chain subfamily of kinesin motor proteins. Extensive alternative splicing produces isoforms with different C-termini that are proposed to bind to different cargos; however, the full-length nature and/or biological validity of most of these variants have not been determined. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000555055.6. 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
	XRCC3	NM_005432.4	MANE Select	c.-318+1026C>T		intron	N/A	NP_005423.1
	XRCC3	NM_001100118.2		c.-261+1026C>T		intron	N/A	NP_001093588.1
	XRCC3	NM_001100119.2		c.-355+1026C>T		intron	N/A	NP_001093589.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XRCC3	ENST00000555055.6	TSL:1 MANE Select	c.-318+1026C>T		intron	N/A	ENSP00000452598.1
	XRCC3	ENST00000352127.11	TSL:1	c.-261+1026C>T		intron	N/A	ENSP00000343392.7
	XRCC3	ENST00000554913.5	TSL:2	c.-290+1026C>T		intron	N/A	ENSP00000451362.1

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

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AF: 0.125 AC: 1 AN: 8

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 1 AN: 4

East Asian (EAS) AF: 0.375 AC: 3 AN: 8

South Asian (SAS) AF: 0.125 AC: 1 AN: 8

European-Finnish (FIN) AF: 0.250 AC: 1 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.361 AC: 78 AN: 216

Other (OTH) AF: 0.333 AC: 6 AN: 18

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

African (AFR) AF: 0.160 AC: 6589 AN: 41134

American (AMR) AF: 0.290 AC: 4410 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.216 AC: 750 AN: 3468

East Asian (EAS) AF: 0.346 AC: 1769 AN: 5116

South Asian (SAS) AF: 0.200 AC: 955 AN: 4768

European-Finnish (FIN) AF: 0.433 AC: 4503 AN: 10400

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.335 AC: 22720 AN: 67738

Other (OTH) AF: 0.263 AC: 553 AN: 2102

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.5
DANN	Benign	0.56
PhyloP100		0.90
PromoterAI		0.00060	Neutral
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: rs3212024; hg19: chr14-104180735;