Variant 19-51079661-C-G 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_001369775.2(KLK14):c.254G>C(p.Trp85Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000174 in 1,435,034 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

KLK14
NM_001369775.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.29

Variant links:

Genes affected

KLK14 (HGNC:6362): (kallikrein related peptidase 14) This gene encodes a member of the kallikrein subfamily of serine proteases that have diverse physiological functions such as regulation of blood pressure and desquamation. The altered expression of this gene is implicated in the progression of different cancers including breast and prostate tumors. The encoded protein is a precursor that is proteolytically processed to generate the functional enzyme. This gene is one of the fifteen kallikrein subfamily members located in a cluster on chromosome 19. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2015]

KLK14 links:

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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=0.07007977).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLK14	NM_001369775.2 linkuse as main transcript	c.254G>C	p.Trp85Ser	missense_variant	4/6	ENST00000650543.2	NP_001356704.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
KLK14	ENST00000650543.2 linkuse as main transcript	c.254G>C	p.Trp85Ser	missense_variant	4/6		NM_001369775.2	ENSP00000497141	P1
KLK14	ENST00000156499.7 linkuse as main transcript	c.254G>C	p.Trp85Ser	missense_variant	5/8	1		ENSP00000156499	P1
KLK14	ENST00000391802.1 linkuse as main transcript	c.302G>C	p.Trp101Ser	missense_variant	5/7	5		ENSP00000375678

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000101

AC:

AN:

198134

Hom.:

AF XY:

0.00

AC XY:

AN XY:

107702

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000139

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000174

AC:

AN:

1435034

Hom.:

Cov.:

AF XY:

0.0000155

AC XY:

AN XY:

711876

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000654

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000831

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

May 12, 2024

The c.302G>C (p.W101S) alteration is located in exon 5 (coding exon 4) of the KLK14 gene. This alteration results from a G to C substitution at nucleotide position 302, causing the tryptophan (W) at amino acid position 101 to be replaced by a serine (S). 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

0.18

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.27

.;T;.

Eigen

Benign

-0.85

Eigen_PC

Benign

-0.65

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.037

.;T;T

M_CAP

Benign

0.020

MetaRNN

Benign

0.070

T;T;T

MetaSVM

Benign

-0.77

MutationAssessor

Benign

-0.47

.;N;.

MutationTaster

Benign

0.94

D;D

PrimateAI

Benign

0.32

PROVEAN

Uncertain

-3.4

.;D;.

REVEL

Benign

0.23

Sift

Benign

0.42

.;T;.

Sift4G

Benign

0.49

.;T;.

Polyphen

0.014

.;B;.

Vest4

0.25

MutPred

0.42

.;Gain of disorder (P = 3e-04);.;

MVP

0.62

MPC

0.25

ClinPred

0.076

GERP RS

2.8

Varity_R

0.40

gMVP

0.72

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