Variant 19-45345732-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_177417.3(KLC3):c.191T>C(p.Leu64Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000239 in 1,559,588 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000086 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00026 ( 1 hom. )

Consequence

KLC3
NM_177417.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.64

Variant links:

Genes affected

KLC3 (HGNC:20717): (kinesin light chain 3) This gene encodes a member of the kinesin light chain gene family. Kinesins are molecular motors involved in the transport of cargo along microtubules, and are composed of two kinesin heavy chain (KHC) and two kinesin light chain (KLC) molecules. KLCs are thought to typically be involved in binding cargo and regulating kinesin activity. In the rat, a protein similar to this gene product is expressed in post-meiotic spermatids, where it associates with structural components of sperm tails and mitochondria. [provided by RefSeq, Jul 2008]

KLC3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15283543).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLC3	NM_177417.3 linkuse as main transcript	c.191T>C	p.Leu64Pro	missense_variant	2/13	ENST00000391946.7	NP_803136.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLC3	ENST00000391946.7 linkuse as main transcript	c.191T>C	p.Leu64Pro	missense_variant	2/13	1	NM_177417.3	ENSP00000375810	P4	Q6P597-1

Frequencies

GnomAD3 genomes

AF:

0.0000858

AC:

AN:

151448

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000486

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000577

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.000480

GnomAD3 exomes

AF:

0.000112

AC:

AN:

161194

Hom.:

AF XY:

0.000127

AC XY:

AN XY:

86326

show subpopulations

Gnomad AFR exome

AF:

0.000116

Gnomad AMR exome

AF:

0.000119

Gnomad ASJ exome

AF:

0.000593

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000142

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000256

AC:

360

AN:

1408140

Hom.:

Cov.:

AF XY:

0.000240

AC XY:

167

AN XY:

695364

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000825

Gnomad4 ASJ exome

AF:

0.000436

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000403

Gnomad4 NFE exome

AF:

0.000309

Gnomad4 OTH exome

AF:

0.000154

GnomAD4 genome

AF:

0.0000858

AC:

AN:

151448

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

73912

show subpopulations

Gnomad4 AFR

AF:

0.0000486

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000577

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.000480

Alfa

AF:

0.000113

Hom.:

Bravo

AF:

0.000113

ExAC

AF:

0.0000705

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 23, 2024

The c.191T>C (p.L64P) alteration is located in exon 2 (coding exon 1) of the KLC3 gene. This alteration results from a T to C substitution at nucleotide position 191, causing the leucine (L) at amino acid position 64 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.017

BayesDel_noAF

Uncertain

-0.010

CADD

Pathogenic

DANN

Benign

0.89

DEOGEN2

Benign

0.079

.;T;.;.;.;.

Eigen

Benign

-0.0077

Eigen_PC

Benign

0.013

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.62

T;T;T;T;T;T

M_CAP

Uncertain

0.18

MetaRNN

Benign

0.15

T;T;T;T;T;T

MetaSVM

Benign

-0.50

MutationAssessor

Benign

1.0

.;L;L;.;.;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-1.7

.;N;.;.;.;N

REVEL

Uncertain

0.55

Sift

Benign

0.39

.;T;.;.;.;T

Sift4G

Benign

0.34

T;T;T;T;T;T

Polyphen

0.98, 0.99

.;D;D;.;.;D

Vest4

0.70, 0.70, 0.54

MutPred

0.36

Gain of loop (P = 0.0045);Gain of loop (P = 0.0045);Gain of loop (P = 0.0045);Gain of loop (P = 0.0045);Gain of loop (P = 0.0045);.;

MVP

0.82

MPC

0.013

ClinPred

0.042

GERP RS

3.4

Varity_R

0.64

gMVP

0.53

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over