rs3212112

Variant names:

• chr14-103699345-A-C
• rs3212112
• NM_001394837.1:c.1849-1310A>C

Your query was ambiguous. Multiple possible variants found:

• chr14-103699345-A-C
• chr14-103699345-A-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001394837.1(KLC1):​c.1849-1310A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00481 in 1,585,862 control chromosomes in the GnomAD database, including 236 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.021 (108 hom., cov: 33)
  • Exomes 𝑓: 0.0031 (128 hom.)
• Consequence: KLC1 NM_001394837.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.44
• Publications: 4 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 14-103699345-A-C is Benign according to our data. Variant chr14-103699345-A-C is described in ClinVar as Benign. ClinVar VariationId is 2739870.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0665 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394837.1. 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
	KLC1	NM_001394837.1	MANE Select	c.1849-1310A>C		intron	N/A	NP_001381766.1
	XRCC3	NM_005432.4	MANE Select	c.774+19T>G		intron	N/A	NP_005423.1
	KLC1	NM_001394832.1		c.1924-1310A>C		intron	N/A	NP_001381761.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLC1	ENST00000334553.11	TSL:5 MANE Select	c.1849-1310A>C		intron	N/A	ENSP00000334523.6
	XRCC3	ENST00000555055.6	TSL:1 MANE Select	c.774+19T>G		intron	N/A	ENSP00000452598.1
	KLC1	ENST00000348520.10	TSL:1	c.1651-1310A>C		intron	N/A	ENSP00000341154.6

Frequencies

GnomAD3 genomes AF: 0.0209 AC: 3178 AN: 151884 Hom.: 107 Cov.: 33

Gnomad AFR AF: 0.0684

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00924

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0211

Gnomad SAS AF: 0.00643

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.000456

Gnomad OTH AF: 0.0153

GnomAD2 exomes AF: 0.00705 AC: 1434 AN: 203346 AF XY: 0.00584

Gnomad AFR exome AF: 0.0683

Gnomad AMR exome AF: 0.00417

Gnomad ASJ exome AF: 0.000109

Gnomad EAS exome AF: 0.0250

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000342

Gnomad OTH exome AF: 0.00384

GnomAD4 exome AF: 0.00309 AC: 4428 AN: 1433860 Hom.: 128 Cov.: 31 AF XY: 0.00287 AC XY: 2041 AN XY: 711400

African (AFR) AF: 0.0776 AC: 2535 AN: 32670

American (AMR) AF: 0.00474 AC: 189 AN: 39838

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25622

East Asian (EAS) AF: 0.0177 AC: 674 AN: 38014

South Asian (SAS) AF: 0.00357 AC: 299 AN: 83662

European-Finnish (FIN) AF: 0.0000198 AC: 1 AN: 50498

Middle Eastern (MID) AF: 0.00527 AC: 27 AN: 5120

European-Non Finnish (NFE) AF: 0.000265 AC: 291 AN: 1099206

Other (OTH) AF: 0.00696 AC: 412 AN: 59230

GnomAD4 genome AF: 0.0210 AC: 3195 AN: 152002 Hom.: 108 Cov.: 33 AF XY: 0.0211 AC XY: 1568 AN XY: 74280

African (AFR) AF: 0.0687 AC: 2845 AN: 41440

American (AMR) AF: 0.00922 AC: 141 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.0212 AC: 109 AN: 5142

South Asian (SAS) AF: 0.00644 AC: 31 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10594

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.000456 AC: 31 AN: 67950

Other (OTH) AF: 0.0152 AC: 32 AN: 2108

Alfa AF: 0.0133 Hom.: 8

Bravo AF: 0.0246

Asia WGS AF: 0.0160 AC: 57 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.42
DANN	Benign	0.62
PhyloP100		-2.4
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: rs3212112; hg19: chr14-104165682; COSMIC: COSV104639390;