rs3212079

Variant names:

• chr14-103704128-G-A
• rs3212079
• ENST00000348520.10:c.*2929G>A

Variant summary

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

The ENST00000348520.10(KLC1):​c.*2929G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0526 in 152,476 control chromosomes in the GnomAD database, including 243 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 0.053 (242 hom., cov: 33)
  • Exomes 𝑓: 0.074 (1 hom.)
• Consequence: KLC1 ENST00000348520.10 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.315
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0857 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XRCC3	NM_005432.4	c.407-801C>T		intron_variant	Intron 6 of 9	ENST00000555055.6	NP_005423.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XRCC3	ENST00000555055.6	c.407-801C>T		intron_variant	Intron 6 of 9	1	NM_005432.4	ENSP00000452598.1

Frequencies

GnomAD3 genomes AF: 0.0527 AC: 8014 AN: 152170 Hom.: 244 Cov.: 33

Gnomad AFR AF: 0.0384

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.0450

Gnomad ASJ AF: 0.0567

Gnomad EAS AF: 0.00366

Gnomad SAS AF: 0.0929

Gnomad FIN AF: 0.0242

Gnomad MID AF: 0.0955

Gnomad NFE AF: 0.0668

Gnomad OTH AF: 0.0617

GnomAD4 exome AF: 0.0745 AC: 14 AN: 188 Hom.: 1 Cov.: 0 AF XY: 0.0517 AC XY: 6 AN XY: 116

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AF: 0.00 AC: 0 AN: 4

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AF: 0.167 AC: 1 AN: 6

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0759 AC: 12 AN: 158

Other (OTH) AF: 0.167 AC: 1 AN: 6

GnomAD4 genome AF: 0.0526 AC: 8011 AN: 152288 Hom.: 242 Cov.: 33 AF XY: 0.0510 AC XY: 3797 AN XY: 74472

African (AFR) AF: 0.0384 AC: 1596 AN: 41540

American (AMR) AF: 0.0450 AC: 688 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0567 AC: 197 AN: 3472

East Asian (EAS) AF: 0.00348 AC: 18 AN: 5176

South Asian (SAS) AF: 0.0928 AC: 448 AN: 4828

European-Finnish (FIN) AF: 0.0242 AC: 257 AN: 10628

Middle Eastern (MID) AF: 0.0890 AC: 26 AN: 292

European-Non Finnish (NFE) AF: 0.0668 AC: 4547 AN: 68028

Other (OTH) AF: 0.0611 AC: 129 AN: 2112

Alfa AF: 0.0649 Hom.: 575

Bravo AF: 0.0527

Asia WGS AF: 0.0550 AC: 191 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.8
DANN	Benign	0.71
PhyloP100		-0.32
Mutation Taster		=100/0	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: rs3212079; hg19: chr14-104170465;