Variant 14-103711849-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.08

Variant links:

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]

KLC1 links:

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]

XRCC3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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/exons	MANE	UniProt
XRCC3	NM_005432.4 linkuse as main transcript	c.-260-282T>C		intron_variant		ENST00000555055.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XRCC3	ENST00000555055.6 linkuse as main transcript	c.-260-282T>C		intron_variant		1	NM_005432.4	P1

Frequencies

GnomAD3 genomes

AF:

0.282

AC:

42897

AN:

151982

Hom.:

6802

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.299

AC:

20692

AN:

69124

Hom.:

3275

AF XY:

0.294

AC XY:

10548

AN XY:

35824

show subpopulations

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 SAS exome

AF:

0.194

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.:

AF XY:

0.289

AC XY:

36458

AN XY:

126096

show subpopulations

Gnomad4 AFR exome

AF:

0.151

Gnomad4 AMR exome

AF:

0.324

Gnomad4 ASJ exome

AF:

0.205

Gnomad4 EAS exome

AF:

0.367

Gnomad4 SAS exome

AF:

0.203

Gnomad4 FIN exome

AF:

0.412

Gnomad4 NFE exome

AF:

0.334

Gnomad4 OTH exome

AF:

0.300

GnomAD4 genome

AF:

0.282

AC:

42922

AN:

152100

Hom.:

6813

Cov.:

AF XY:

0.284

AC XY:

21082

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.158

Gnomad4 AMR

AF:

0.291

Gnomad4 ASJ

AF:

0.217

Gnomad4 EAS

AF:

0.362

Gnomad4 SAS

AF:

0.203

Gnomad4 FIN

AF:

0.433

Gnomad4 NFE

AF:

0.336

Gnomad4 OTH

AF:

0.265

Alfa

AF:

0.295

Hom.:

1395

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

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over