Variant chr19-51032073-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001370125.1(KLK12):c.260G>A(p.Arg87Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000592 in 1,604,382 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000048 ( 0 hom. )

Consequence

KLK12
NM_001370125.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.618

Variant links:

Genes affected

KLK12 (HGNC:6360): (kallikrein related peptidase 12) Kallikreins are a subgroup of serine proteases having diverse physiological functions. Growing evidence suggests that many kallikreins are implicated in carcinogenesis and some have potential as novel cancer and other disease biomarkers. This gene is one of the fifteen kallikrein subfamily members located in a cluster on chromosome 19. Alternate splicing of this gene results in three transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

KLK12 links:

ENSG00000268906 (HGNC:):

ENSG00000268906 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.28547433).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLK12	NM_001370125.1 linkuse as main transcript	c.260G>A	p.Arg87Gln	missense_variant	4/6	ENST00000684732.1	NP_001357054.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLK12	ENST00000684732.1 linkuse as main transcript	c.260G>A	p.Arg87Gln	missense_variant	4/6		NM_001370125.1	ENSP00000508282.1		Q9UKR0-1

Frequencies

GnomAD3 genomes

AF:

0.000171

AC:

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000507

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000117

AC:

AN:

230744

Hom.:

AF XY:

0.000127

AC XY:

AN XY:

125922

show subpopulations

Gnomad AFR exome

AF:

0.000960

Gnomad AMR exome

AF:

0.0000602

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000574

Gnomad SAS exome

AF:

0.000340

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000482

AC:

AN:

1452100

Hom.:

Cov.:

AF XY:

0.0000595

AC XY:

AN XY:

722242

show subpopulations

Gnomad4 AFR exome

AF:

0.000481

Gnomad4 AMR exome

AF:

0.0000684

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000178

Gnomad4 SAS exome

AF:

0.000258

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000162

Gnomad4 OTH exome

AF:

0.0000500

GnomAD4 genome

AF:

0.000164

AC:

AN:

152282

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.000481

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.0000422

Hom.:

Bravo

AF:

0.000189

ESP6500AA

AF:

0.000682

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000116

AC:

Asia WGS

AF:

0.000577

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

Oct 03, 2024

The c.260G>A (p.R87Q) alteration is located in exon 4 (coding exon 3) of the KLK12 gene. This alteration results from a G to A substitution at nucleotide position 260, causing the arginine (R) at amino acid position 87 to be replaced by a glutamine (Q). 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

0.20

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.11

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.25

T;T;.

Eigen

Benign

0.011

Eigen_PC

Benign

-0.031

FATHMM_MKL

Benign

0.31

LIST_S2

Benign

0.76

.;T;T

M_CAP

Uncertain

0.089

MetaRNN

Benign

0.29

T;T;T

MetaSVM

Uncertain

0.62

MutationAssessor

Benign

0.99

L;L;L

PrimateAI

Benign

0.34

PROVEAN

Benign

-1.1

N;N;N

REVEL

Uncertain

0.51

Sift

Benign

0.15

T;T;T

Sift4G

Uncertain

0.050

T;T;T

Polyphen

0.97

D;D;P

Vest4

0.51

MVP

0.88

MPC

0.37

ClinPred

0.047

GERP RS

4.1

Varity_R

0.093

gMVP

0.62

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

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