chr14-103712977-T-C

Variant names:

• chr14-103712977-T-C
• rs861529
• ENST00000348520.10:c.*11778T>C

Variant summary

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

The ENST00000348520.10(KLC1):​c.*11778T>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 0.908 in 152,442 control chromosomes in the GnomAD database, including 63,331 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 0.91 (63256 hom., cov: 34)
  • Exomes 𝑓: 0.96 (75 hom.)
• Consequence: KLC1 ENST00000348520.10 3_prime_UTR
• Scores: Splicing: ADA: 0.00003789
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17
• Publications: 8 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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.963 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XRCC3	NM_005432.4	c.-317-46A>G		intron_variant	Intron 1 of 9	ENST00000555055.6	NP_005423.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XRCC3	ENST00000555055.6	c.-317-46A>G		intron_variant	Intron 1 of 9	1	NM_005432.4	ENSP00000452598.1

Frequencies

GnomAD3 genomes AF: 0.909 AC: 138246 AN: 152160 Hom.: 63234 Cov.: 34

Gnomad AFR AF: 0.827

Gnomad AMI AF: 0.977

Gnomad AMR AF: 0.804

Gnomad ASJ AF: 0.917

Gnomad EAS AF: 0.923

Gnomad SAS AF: 0.895

Gnomad FIN AF: 0.982

Gnomad MID AF: 0.921

Gnomad NFE AF: 0.969

Gnomad OTH AF: 0.908

GnomAD4 exome AF: 0.957 AC: 157 AN: 164 Hom.: 75 Cov.: 0 AF XY: 0.975 AC XY: 117 AN XY: 120

African (AFR) AF: 1.00 AC: 2 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 1.00 AC: 2 AN: 2

South Asian (SAS) AF: 1.00 AC: 10 AN: 10

European-Finnish (FIN) AF: 1.00 AC: 20 AN: 20

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.949 AC: 112 AN: 118

Other (OTH) AF: 0.917 AC: 11 AN: 12

GnomAD4 genome AF: 0.908 AC: 138321 AN: 152278 Hom.: 63256 Cov.: 34 AF XY: 0.906 AC XY: 67466 AN XY: 74450

African (AFR) AF: 0.826 AC: 34335 AN: 41554

American (AMR) AF: 0.803 AC: 12284 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.917 AC: 3183 AN: 3472

East Asian (EAS) AF: 0.923 AC: 4771 AN: 5170

South Asian (SAS) AF: 0.896 AC: 4328 AN: 4828

European-Finnish (FIN) AF: 0.982 AC: 10430 AN: 10622

Middle Eastern (MID) AF: 0.915 AC: 269 AN: 294

European-Non Finnish (NFE) AF: 0.969 AC: 65910 AN: 68016

Other (OTH) AF: 0.907 AC: 1920 AN: 2116

Alfa AF: 0.945 Hom.: 23545

Bravo AF: 0.888

Asia WGS AF: 0.882 AC: 3068 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.47
DANN	Benign	0.29
PhyloP100		-1.2
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000038
SpliceAI score (max)		0.020		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: rs861529; hg19: chr14-104179314;