rs3212090

chr14-103702526-C-T

Variant summary

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

The ENST00000348520.10(KLC1):c.*1327C>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 0.281 in 153,380 control chromosomes in the GnomAD database, including 6,791 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 (6733 hom., cov: 33)
  • Exomes 𝑓: 0.31 (58 hom.)
• Consequence: KLC1 ENST00000348520.10 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.185

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.344 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XRCC3	NM_005432.4	c.561+647G>A		intron_variant		ENST00000555055.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XRCC3	ENST00000555055.6	c.561+647G>A		intron_variant		1	NM_005432.4	P1

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42620 AN: 152048 Hom.: 6720 Cov.: 33

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.310

Gnomad AMR AF: 0.289

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.358

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.432

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.262

GnomAD4 exome AF: 0.309 AC: 375 AN: 1212 Hom.: 58 Cov.: 0 AF XY: 0.294 AC XY: 184 AN XY: 626

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.309

Gnomad4 ASJ exome AF: 0.250

Gnomad4 EAS exome AF: 0.167

Gnomad4 SAS exome AF: 0.129

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.330

Gnomad4 OTH exome AF: 0.354

GnomAD4 genome AF: 0.280 AC: 42649 AN: 152168 Hom.: 6733 Cov.: 33 AF XY: 0.282 AC XY: 20957 AN XY: 74396

Gnomad4 AFR AF: 0.157

Gnomad4 AMR AF: 0.289

Gnomad4 ASJ AF: 0.217

Gnomad4 EAS AF: 0.357

Gnomad4 SAS AF: 0.201

Gnomad4 FIN AF: 0.432

Gnomad4 NFE AF: 0.333

Gnomad4 OTH AF: 0.263

Alfa AF: 0.308 Hom.: 7750

Bravo AF: 0.264

Asia WGS AF: 0.262 AC: 909 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	1.0
Dann	Benign	0.50

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: rs3212090; hg19: chr14-104168863;