Variant chr19-51015458-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_145888.3(KLK10):c.637A>G(p.Met213Val) variant causes a missense change. The variant allele was found at a frequency of 0.00016 in 1,613,622 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00017 ( 0 hom. )

Consequence

KLK10
NM_145888.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.21

Variant links:

Genes affected

KLK10 (HGNC:6358): (kallikrein related peptidase 10) 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. Its encoded protein is secreted and may play a role in suppression of tumorigenesis in breast and prostate cancers. Alternate splicing of this gene results in multiple transcript variants encoding the same protein. [provided by RefSeq, Jul 2008]

KLK10 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.93

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLK10	NM_145888.3 link	c.637A>G	p.Met213Val	missense_variant	5/6	ENST00000358789.8	NP_665895.1	O43240

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLK10	ENST00000358789.8 link	c.637A>G	p.Met213Val	missense_variant	5/6	1	NM_145888.3	ENSP00000351640.2		O43240

Frequencies

GnomAD3 genomes

AF:

0.0000724

AC:

AN:

151854

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.000480

GnomAD3 exomes

AF:

0.0000676

AC:

AN:

251416

Hom.:

AF XY:

0.0000589

AC XY:

AN XY:

135876

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000149

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000169

AC:

247

AN:

1461768

Hom.:

Cov.:

AF XY:

0.000168

AC XY:

122

AN XY:

727204

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000208

Gnomad4 OTH exome

AF:

0.000248

GnomAD4 genome

AF:

0.0000724

AC:

AN:

151854

Hom.:

Cov.:

AF XY:

0.0000539

AC XY:

AN XY:

74162

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.000480

Alfa

AF:

0.000174

Hom.:

Bravo

AF:

0.0000642

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.0000741

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000237

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

Mar 20, 2023

The c.637A>G (p.M213V) alteration is located in exon 5 (coding exon 4) of the KLK10 gene. This alteration results from a A to G substitution at nucleotide position 637, causing the methionine (M) at amino acid position 213 to be replaced by a valine (V). 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

Uncertain

0.56

BayesDel_addAF

Uncertain

0.13

BayesDel_noAF

Pathogenic

0.21

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.52

D;D;D

Eigen

Uncertain

0.60

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.78

.;T;.

M_CAP

Pathogenic

0.30

MetaRNN

Pathogenic

0.93

D;D;D

MetaSVM

Pathogenic

0.98

MutationAssessor

Uncertain

2.8

M;M;M

PrimateAI

Uncertain

0.52

PROVEAN

Uncertain

-3.9

D;D;D

REVEL

Pathogenic

0.76

Sift

Pathogenic

0.0

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

1.0

D;D;D

Vest4

0.73

MVP

1.0

MPC

0.70

ClinPred

0.74

GERP RS

4.5

Varity_R

0.88

gMVP

0.81

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