rs1014150030

Variant names:

• chr19-50826889-G-A
• NM_017509.4:c.470C>T

Your query was ambiguous. Multiple possible variants found:

• chr19-50826889-G-A
• chr19-50826889-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_017509.4(KLK15):​c.470C>T​(p.Pro157Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/20 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: not found (cov: 32)
• Consequence: KLK15 NM_017509.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.51

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]

ACMG classification

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=0.12285501).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLK15	NM_017509.4	c.470C>T	p.Pro157Leu	missense_variant	Exon 4 of 6	ENST00000598239.6	NP_059979.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLK15	ENST00000598239.6	c.470C>T	p.Pro157Leu	missense_variant	Exon 4 of 6	1	NM_017509.4	ENSP00000469315.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.060	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	17
DANN	Benign	0.96
DEOGEN2	Uncertain	0.45	.;T;.
Eigen	Benign	-0.99
Eigen_PC	Benign	-0.99
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.60	T;T;T
M_CAP	Benign	0.066	D
MetaRNN	Benign	0.12	T;T;T
MetaSVM	Benign	-0.62	T
MutationAssessor	Benign	0.34	.;N;.
PrimateAI	Benign	0.26	T
REVEL	Benign	0.22
Sift4G	Uncertain	0.055	T;T;D
Polyphen		0.0010	.;B;.
Vest4		0.18
MutPred		0.40		.;Loss of relative solvent accessibility (P = 0.0186);.;
MVP		0.81
MPC		0.41
ClinPred		0.26	T
GERP RS		0.84
Varity_R		0.14
gMVP		0.69

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-51330145;