Genetic Variant KLK15:p.Pro157Ala (chr19-50826890-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_017509.4(KLK15):c.469C>G(p.Pro157Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000142 in 1,409,722 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P157R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

KLK15
NM_017509.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0620

Publications

0 publications found

Variant links:

Genes affected

KLK15 (HGNC:20453): (kallikrein related peptidase 15) 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. In prostate cancer, this gene has increased expression, which indicates its possible use as a diagnostic or prognostic marker for prostate cancer. The gene contains multiple polyadenylation sites and alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2008]

KLK15 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.106684655).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017509.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KLK15	NM_017509.4	MANE Select	c.469C>G	p.Pro157Ala	missense	Exon 4 of 6	NP_059979.2
KLK15	NM_001277081.2		c.466C>G	p.Pro156Ala	missense	Exon 4 of 6	NP_001264010.1	Q9H2R5-5
KLK15	NM_001277082.2		c.466C>G	p.Pro156Ala	missense	Exon 4 of 5	NP_001264011.1	M0R0D7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KLK15	ENST00000598239.6	TSL:1 MANE Select	c.469C>G	p.Pro157Ala	missense	Exon 4 of 6	ENSP00000469315.1	Q9H2R5-1
KLK15	ENST00000596931.5	TSL:1	c.466C>G	p.Pro156Ala	missense	Exon 3 of 4	ENSP00000471164.1	M0R0D7
KLK15	ENST00000601680.1	TSL:1	n.469C>G		non_coding_transcript_exon	Exon 3 of 4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000142

AC:

AN:

1409722

Hom.:

Cov.:

AF XY:

0.00000144

AC XY:

AN XY:

694942

show subpopulations

African (AFR)

AF:

0.0000310

AC:

AN:

32254

American (AMR)

AF:

0.00

AC:

AN:

39262

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22566

East Asian (EAS)

AF:

0.00

AC:

AN:

39218

South Asian (SAS)

AF:

0.00

AC:

AN:

77574

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50572

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5530

European-Non Finnish (NFE)

AF:

9.22e-7

AC:

AN:

1084656

Other (OTH)

AF:

0.00

AC:

AN:

58090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.087

BayesDel_noAF

Benign

-0.36

CADD

Benign

9.0

(source)

DANN

Benign

0.65

DEOGEN2

Uncertain

0.45

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.51

M_CAP

Benign

0.031

MetaRNN

Benign

0.11

MetaSVM

Benign

-0.72

MutationAssessor

Benign

0.14

PhyloP100

0.062

PrimateAI

Benign

0.25

REVEL

Benign

0.23

Sift4G

Uncertain

0.015

Polyphen

0.0020

Vest4

0.27

MutPred

0.29

Loss of glycosylation at P157 (P = 0.0203)

MVP

0.76

MPC

0.39

ClinPred

0.12

GERP RS

-2.1

Varity_R

0.074

gMVP

0.61

Mutation Taster

=98/2

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over