rs3212112

chr14-103699345-A-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001394837.1(KLC1):c.1849-1310A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00481 in 1,585,862 control chromosomes in the GnomAD database, including 236 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.021 (108 hom., cov: 33)
  • Exomes 𝑓: 0.0031 (128 hom.)
• Consequence: KLC1 NM_001394837.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.44

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 14-103699345-A-C is Benign according to our data. Variant chr14-103699345-A-C is described in ClinVar as [Benign]. Clinvar id is 2739870.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0665 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KLC1	NM_001394837.1	c.1849-1310A>C		intron_variant		ENST00000334553.11
XRCC3	NM_005432.4	c.774+19T>G		intron_variant		ENST00000555055.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KLC1	ENST00000334553.11	c.1849-1310A>C		intron_variant		5	NM_001394837.1
XRCC3	ENST00000555055.6	c.774+19T>G		intron_variant		1	NM_005432.4	P1

Frequencies

GnomAD3 genomes AF: 0.0209 AC: 3178 AN: 151884 Hom.: 107 Cov.: 33

Gnomad AFR AF: 0.0684

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00924

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0211

Gnomad SAS AF: 0.00643

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.000456

Gnomad OTH AF: 0.0153

GnomAD3 exomes AF: 0.00705 AC: 1434 AN: 203346 Hom.: 39 AF XY: 0.00584 AC XY: 647 AN XY: 110744

Gnomad AFR exome AF: 0.0683

Gnomad AMR exome AF: 0.00417

Gnomad ASJ exome AF: 0.000109

Gnomad EAS exome AF: 0.0250

Gnomad SAS exome AF: 0.00352

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000342

Gnomad OTH exome AF: 0.00384

GnomAD4 exome AF: 0.00309 AC: 4428 AN: 1433860 Hom.: 128 Cov.: 31 AF XY: 0.00287 AC XY: 2041 AN XY: 711400

Gnomad4 AFR exome AF: 0.0776

Gnomad4 AMR exome AF: 0.00474

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0177

Gnomad4 SAS exome AF: 0.00357

Gnomad4 FIN exome AF: 0.0000198

Gnomad4 NFE exome AF: 0.000265

Gnomad4 OTH exome AF: 0.00696

GnomAD4 genome AF: 0.0210 AC: 3195 AN: 152002 Hom.: 108 Cov.: 33 AF XY: 0.0211 AC XY: 1568 AN XY: 74280

Gnomad4 AFR AF: 0.0687

Gnomad4 AMR AF: 0.00922

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0212

Gnomad4 SAS AF: 0.00644

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000456

Gnomad4 OTH AF: 0.0152

Alfa AF: 0.0117 Hom.: 8

Bravo AF: 0.0246

Asia WGS AF: 0.0160 AC: 57 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 07, 2023

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.42
Dann	Benign	0.62

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: rs3212112; hg19: chr14-104165682; COSMIC: COSV104639390; COSMIC: COSV104639390;