chr14-103707786-T-C

Variant names:

• chr14-103707786-T-C
• rs861530
• ENST00000348520.10:c.*6587T>C

Variant summary

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

The ENST00000348520.10(KLC1):​c.*6587T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.64 in 192,216 control chromosomes in the GnomAD database, including 40,241 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 0.64 (31820 hom., cov: 36)
  • Exomes 𝑓: 0.63 (8421 hom.)
• Consequence: KLC1 ENST00000348520.10 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09
• Publications: 27 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=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.704 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000348520.10. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XRCC3	NM_005432.4	MANE Select	c.194-571A>G		intron	N/A	NP_005423.1
	XRCC3	NM_001100118.2		c.194-571A>G		intron	N/A	NP_001093588.1
	XRCC3	NM_001100119.2		c.194-571A>G		intron	N/A	NP_001093589.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLC1	ENST00000348520.10	TSL:1	c.*6587T>C		3_prime_UTR	Exon 15 of 15	ENSP00000341154.6
	XRCC3	ENST00000555055.6	TSL:1 MANE Select	c.194-571A>G		intron	N/A	ENSP00000452598.1
	XRCC3	ENST00000352127.11	TSL:1	c.194-571A>G		intron	N/A	ENSP00000343392.7

Frequencies

GnomAD3 genomes AF: 0.642 AC: 97677 AN: 152076 Hom.: 31788 Cov.: 36

Gnomad AFR AF: 0.583

Gnomad AMI AF: 0.708

Gnomad AMR AF: 0.571

Gnomad ASJ AF: 0.630

Gnomad EAS AF: 0.470

Gnomad SAS AF: 0.445

Gnomad FIN AF: 0.721

Gnomad MID AF: 0.618

Gnomad NFE AF: 0.710

Gnomad OTH AF: 0.624

GnomAD4 exome AF: 0.633 AC: 25344 AN: 40022 Hom.: 8421 Cov.: 0 AF XY: 0.618 AC XY: 12739 AN XY: 20624

African (AFR) AF: 0.569 AC: 394 AN: 692

American (AMR) AF: 0.559 AC: 1955 AN: 3496

Ashkenazi Jewish (ASJ) AF: 0.603 AC: 470 AN: 780

East Asian (EAS) AF: 0.438 AC: 1088 AN: 2484

South Asian (SAS) AF: 0.455 AC: 2404 AN: 5288

European-Finnish (FIN) AF: 0.706 AC: 904 AN: 1280

Middle Eastern (MID) AF: 0.590 AC: 79 AN: 134

European-Non Finnish (NFE) AF: 0.701 AC: 16691 AN: 23798

Other (OTH) AF: 0.657 AC: 1359 AN: 2070

GnomAD4 genome AF: 0.642 AC: 97753 AN: 152194 Hom.: 31820 Cov.: 36 AF XY: 0.636 AC XY: 47358 AN XY: 74412

African (AFR) AF: 0.583 AC: 24224 AN: 41524

American (AMR) AF: 0.571 AC: 8739 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.630 AC: 2188 AN: 3472

East Asian (EAS) AF: 0.469 AC: 2421 AN: 5162

South Asian (SAS) AF: 0.447 AC: 2157 AN: 4828

European-Finnish (FIN) AF: 0.721 AC: 7642 AN: 10606

Middle Eastern (MID) AF: 0.627 AC: 183 AN: 292

European-Non Finnish (NFE) AF: 0.710 AC: 48241 AN: 67986

Other (OTH) AF: 0.621 AC: 1312 AN: 2114

Alfa AF: 0.684 Hom.: 11850

Bravo AF: 0.629

Asia WGS AF: 0.423 AC: 1475 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.19
DANN	Benign	0.19
PhyloP100		-1.1
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: rs861530; hg19: chr14-104174123;