rs3212038

Variant names:

• chr14-103711849-A-G
• rs3212038
• ENST00000348520.10:c.*10650A>G

Variant summary

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

The ENST00000348520.10(KLC1):​c.*10650A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 378,392 control chromosomes in the GnomAD database, including 17,702 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 (6813 hom., cov: 33)
  • Exomes 𝑓: 0.30 (10889 hom.)
• Consequence: KLC1 ENST00000348520.10 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08
• Publications: 12 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.348 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XRCC3	NM_005432.4	c.-260-282T>C		intron_variant	Intron 2 of 9	ENST00000555055.6	NP_005423.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XRCC3	ENST00000555055.6	c.-260-282T>C		intron_variant	Intron 2 of 9	1	NM_005432.4	ENSP00000452598.1

Frequencies

GnomAD3 genomes AF: 0.282 AC: 42897 AN: 151982 Hom.: 6802 Cov.: 33

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.311

Gnomad AMR AF: 0.290

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.362

Gnomad SAS AF: 0.202

Gnomad FIN AF: 0.433

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.336

Gnomad OTH AF: 0.264

GnomAD2 exomes AF: 0.299 AC: 20692 AN: 69124 AF XY: 0.294

Gnomad AFR exome AF: 0.149

Gnomad AMR exome AF: 0.328

Gnomad ASJ exome AF: 0.213

Gnomad EAS exome AF: 0.367

Gnomad FIN exome AF: 0.421

Gnomad NFE exome AF: 0.332

Gnomad OTH exome AF: 0.302

GnomAD4 exome AF: 0.300 AC: 67976 AN: 226292 Hom.: 10889 Cov.: 0 AF XY: 0.289 AC XY: 36458 AN XY: 126096

African (AFR) AF: 0.151 AC: 930 AN: 6166

American (AMR) AF: 0.324 AC: 5257 AN: 16236

Ashkenazi Jewish (ASJ) AF: 0.205 AC: 1151 AN: 5606

East Asian (EAS) AF: 0.367 AC: 3154 AN: 8594

South Asian (SAS) AF: 0.203 AC: 9503 AN: 46892

European-Finnish (FIN) AF: 0.412 AC: 3884 AN: 9426

Middle Eastern (MID) AF: 0.210 AC: 164 AN: 782

European-Non Finnish (NFE) AF: 0.334 AC: 40728 AN: 121918

Other (OTH) AF: 0.300 AC: 3205 AN: 10672

GnomAD4 genome AF: 0.282 AC: 42922 AN: 152100 Hom.: 6813 Cov.: 33 AF XY: 0.284 AC XY: 21082 AN XY: 74362

African (AFR) AF: 0.158 AC: 6556 AN: 41524

American (AMR) AF: 0.291 AC: 4444 AN: 15288

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

East Asian (EAS) AF: 0.362 AC: 1869 AN: 5164

South Asian (SAS) AF: 0.203 AC: 978 AN: 4824

European-Finnish (FIN) AF: 0.433 AC: 4576 AN: 10572

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

European-Non Finnish (NFE) AF: 0.336 AC: 22837 AN: 67942

Other (OTH) AF: 0.265 AC: 560 AN: 2112

Alfa AF: 0.291 Hom.: 1405

Bravo AF: 0.267

Asia WGS AF: 0.265 AC: 922 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.13
DANN	Benign	0.45
PhyloP100		-1.1
PromoterAI		0.16	Neutral
Mutation Taster		=299/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3212038; hg19: chr14-104178186;