rs3212092

Variant names:

• chr14-103702307-G-A
• rs3212092
• ENST00000348520.10:c.*1108G>A

Your query was ambiguous. Multiple possible variants found:

• chr14-103702307-G-A
• chr14-103702307-G-C
• chr14-103702307-G-T

Variant summary

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

The ENST00000348520.10(KLC1):​c.*1108G>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 0.0117 in 152,500 control chromosomes in the GnomAD database, including 20 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 0.012 (20 hom., cov: 33)
  • Exomes 𝑓: 0.0075 (0 hom.)
• Consequence: KLC1 ENST00000348520.10 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03
• Publications: 9 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=-0.88).
• BA1: GnomAdExome4 highest subpopulation (EAS) allele frequency = 0.5 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XRCC3	NM_005432.4	MANE Select	c.561+866C>T		intron	N/A	NP_005423.1	O43542
	XRCC3	NM_001100118.2		c.561+866C>T		intron	N/A	NP_001093588.1	Q53XC8
	XRCC3	NM_001100119.2		c.561+866C>T		intron	N/A	NP_001093589.1	O43542

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLC1	ENST00000348520.10	TSL:1	c.*1108G>A		3_prime_UTR	Exon 15 of 15	ENSP00000341154.6	Q07866-1
	XRCC3	ENST00000555055.6	TSL:1 MANE Select	c.561+866C>T		intron	N/A	ENSP00000452598.1	O43542
	XRCC3	ENST00000352127.11	TSL:1	c.561+866C>T		intron	N/A	ENSP00000343392.7	O43542

Frequencies

GnomAD3 genomes AF: 0.0117 AC: 1778 AN: 152248 Hom.: 20 Cov.: 33

Gnomad AFR AF: 0.0205

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00556

Gnomad ASJ AF: 0.00922

Gnomad EAS AF: 0.0419

Gnomad SAS AF: 0.0406

Gnomad FIN AF: 0.00207

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.00510

Gnomad OTH AF: 0.00860

GnomAD4 exome AF: 0.00746 AC: 1 AN: 134 Hom.: 0 Cov.: 0 AF XY: 0.0102 AC XY: 1 AN XY: 98

African (AFR) AF: 0.00 AC: 0 AN: 4

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.500 AC: 1 AN: 2

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 108

Other (OTH) AF: 0.00 AC: 0 AN: 10

GnomAD4 genome AF: 0.0117 AC: 1785 AN: 152366 Hom.: 20 Cov.: 33 AF XY: 0.0124 AC XY: 924 AN XY: 74508

African (AFR) AF: 0.0207 AC: 859 AN: 41590

American (AMR) AF: 0.00555 AC: 85 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00922 AC: 32 AN: 3470

East Asian (EAS) AF: 0.0418 AC: 217 AN: 5190

South Asian (SAS) AF: 0.0400 AC: 193 AN: 4828

European-Finnish (FIN) AF: 0.00207 AC: 22 AN: 10630

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.00510 AC: 347 AN: 68028

Other (OTH) AF: 0.00993 AC: 21 AN: 2114

Alfa AF: 0.00781 Hom.: 7

Bravo AF: 0.0124

Asia WGS AF: 0.0470 AC: 164 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.62
DANN	Benign	0.52
PhyloP100		-1.0
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: rs3212092; hg19: chr14-104168644;