rs12432907

Positions:

• chr14-103702041-C-T

Variant summary

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

The ENST00000348520.10(KLC1):​c.*842C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 152,138 control chromosomes in the GnomAD database, including 4,837 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 0.24 (4835 hom., cov: 32)
  • Exomes 𝑓: 0.17 (2 hom.)
• Consequence: KLC1 ENST00000348520.10 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.52

Genes affected

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]

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.476 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XRCC3	NM_005432.4	c.561+1132G>A		intron_variant		ENST00000555055.6	NP_005423.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XRCC3	ENST00000555055.6	c.561+1132G>A		intron_variant		1	NM_005432.4	ENSP00000452598	P1

Frequencies

GnomAD3 genomes AF: 0.245 AC: 37155 AN: 151936 Hom.: 4828 Cov.: 32

Gnomad AFR AF: 0.257

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.311

Gnomad ASJ AF: 0.246

Gnomad EAS AF: 0.492

Gnomad SAS AF: 0.373

Gnomad FIN AF: 0.241

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.259

GnomAD4 exome AF: 0.167 AC: 14 AN: 84 Hom.: 2 Cov.: 0 AF XY: 0.167 AC XY: 11 AN XY: 66

Gnomad4 AFR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.125

Gnomad4 NFE exome AF: 0.152

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.245 AC: 37180 AN: 152054 Hom.: 4835 Cov.: 32 AF XY: 0.253 AC XY: 18768 AN XY: 74322

Gnomad4 AFR AF: 0.257

Gnomad4 AMR AF: 0.311

Gnomad4 ASJ AF: 0.246

Gnomad4 EAS AF: 0.492

Gnomad4 SAS AF: 0.372

Gnomad4 FIN AF: 0.241

Gnomad4 NFE AF: 0.195

Gnomad4 OTH AF: 0.263

Alfa AF: 0.213 Hom.: 4600

Bravo AF: 0.250

Asia WGS AF: 0.436 AC: 1516 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.90
DANN	Benign	0.33

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: rs12432907; hg19: chr14-104168378;