rs3212090

Variant names:

• chr14-103702526-C-T
• rs3212090
• ENST00000348520.10:c.*1327C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 17 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
XRCC3	NM_005432.4	c.561+647G>A		intron_variant	Intron 7 of 9	ENST00000555055.6	NP_005423.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XRCC3	ENST00000555055.6	c.561+647G>A		intron_variant	Intron 7 of 9	1	NM_005432.4	ENSP00000452598.1

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

African (AFR) AF: 0.00 AC: 0 AN: 8

American (AMR) AF: 0.309 AC: 84 AN: 272

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

East Asian (EAS) AF: 0.167 AC: 3 AN: 18

South Asian (SAS) AF: 0.129 AC: 8 AN: 62

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.330 AC: 262 AN: 794

Other (OTH) AF: 0.354 AC: 17 AN: 48

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

African (AFR) AF: 0.157 AC: 6519 AN: 41512

American (AMR) AF: 0.289 AC: 4427 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.217 AC: 752 AN: 3472

East Asian (EAS) AF: 0.357 AC: 1852 AN: 5182

South Asian (SAS) AF: 0.201 AC: 970 AN: 4826

European-Finnish (FIN) AF: 0.432 AC: 4577 AN: 10588

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.333 AC: 22647 AN: 67976

Other (OTH) AF: 0.263 AC: 555 AN: 2112

Alfa AF: 0.306 Hom.: 11360

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
PhyloP100		-0.18
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: rs3212090; hg19: chr14-104168863;