Genetic Variant NM_017509.4:c.183C>A (chr19-50827676-G-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_017509.4(KLK15):c.183C>A(p.Ala61Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 1,609,950 control chromosomes in the GnomAD database, including 70,848 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.23 ( 5642 hom., cov: 32)

Exomes 𝑓: 0.27 ( 65206 hom. )

Consequence

KLK15
NM_017509.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0960

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 made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP7

Synonymous conserved (PhyloP=-0.096 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.495 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLK15	NM_017509.4 link	c.183C>A	p.Ala61Ala	synonymous_variant	Exon 3 of 6	ENST00000598239.6	NP_059979.2	Q9H2R5-1Q6UBM2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLK15	ENST00000598239.6 link	c.183C>A	p.Ala61Ala	synonymous_variant	Exon 3 of 6	1	NM_017509.4	ENSP00000469315.1		Q9H2R5-1

Frequencies

GnomAD3 genomes

AF:

0.229

AC:

34606

AN:

151166

Hom.:

5625

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0752

Gnomad AMI

AF:

0.187

Gnomad AMR

AF:

0.365

Gnomad ASJ

AF:

0.242

Gnomad EAS

AF:

0.511

Gnomad SAS

AF:

0.274

Gnomad FIN

AF:

0.296

Gnomad MID

AF:

0.146

Gnomad NFE

AF:

0.258

Gnomad OTH

AF:

0.222

GnomAD3 exomes

AF:

0.302

AC:

75202

AN:

249004

Hom.:

14610

AF XY:

0.294

AC XY:

39564

AN XY:

134612

show subpopulations

Gnomad AFR exome

AF:

0.0717

Gnomad AMR exome

AF:

0.508

Gnomad ASJ exome

AF:

0.237

Gnomad EAS exome

AF:

0.509

Gnomad SAS exome

AF:

0.262

Gnomad FIN exome

AF:

0.300

Gnomad NFE exome

AF:

0.257

Gnomad OTH exome

AF:

0.270

GnomAD4 exome

AF:

0.268

AC:

391238

AN:

1458666

Hom.:

65206

Cov.:

AF XY:

0.267

AC XY:

193975

AN XY:

725694

show subpopulations

Gnomad4 AFR exome

AF:

0.0643

Gnomad4 AMR exome

AF:

0.490

Gnomad4 ASJ exome

AF:

0.232

Gnomad4 EAS exome

AF:

0.447

Gnomad4 SAS exome

AF:

0.269

Gnomad4 FIN exome

AF:

0.299

Gnomad4 NFE exome

AF:

0.259

Gnomad4 OTH exome

AF:

0.264

GnomAD4 genome

AF:

0.229

AC:

34645

AN:

151284

Hom.:

5642

Cov.:

AF XY:

0.235

AC XY:

17355

AN XY:

73952

show subpopulations

Gnomad4 AFR

AF:

0.0751

Gnomad4 AMR

AF:

0.366

Gnomad4 ASJ

AF:

0.242

Gnomad4 EAS

AF:

0.511

Gnomad4 SAS

AF:

0.273

Gnomad4 FIN

AF:

0.296

Gnomad4 NFE

AF:

0.258

Gnomad4 OTH

AF:

0.232

Alfa

AF:

0.242

Hom.:

6301

Bravo

AF:

0.229

Asia WGS

AF:

0.398

AC:

1381

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

6.2

DANN

Benign

0.78

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over