19-50825480-C-T

Position:

• chr19-50825480-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017509.4(KLK15):​c.*316G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 194,208 control chromosomes in the GnomAD database, including 6,240 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 0.22 (4693 hom., cov: 31)
  • Exomes 𝑓: 0.25 (1547 hom.)
• Consequence: KLK15 NM_017509.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.324

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.512 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLK15	NM_017509.4	c.*316G>A		3_prime_UTR_variant	6/6	ENST00000598239.6	NP_059979.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLK15	ENST00000598239	c.*316G>A		3_prime_UTR_variant	6/6	1	NM_017509.4	ENSP00000469315.1

Frequencies

GnomAD3 genomes AF: 0.221 AC: 33557 AN: 151830 Hom.: 4671 Cov.: 31

Gnomad AFR AF: 0.0836

Gnomad AMI AF: 0.180

Gnomad AMR AF: 0.352

Gnomad ASJ AF: 0.232

Gnomad EAS AF: 0.528

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.291

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.238

Gnomad OTH AF: 0.212

GnomAD4 exome AF: 0.252 AC: 10670 AN: 42258 Hom.: 1547 Cov.: 0 AF XY: 0.253 AC XY: 5371 AN XY: 21266

Gnomad4 AFR exome AF: 0.0825

Gnomad4 AMR exome AF: 0.407

Gnomad4 ASJ exome AF: 0.216

Gnomad4 EAS exome AF: 0.439

Gnomad4 SAS exome AF: 0.244

Gnomad4 FIN exome AF: 0.287

Gnomad4 NFE exome AF: 0.234

Gnomad4 OTH exome AF: 0.249

GnomAD4 genome AF: 0.221 AC: 33605 AN: 151950 Hom.: 4693 Cov.: 31 AF XY: 0.227 AC XY: 16877 AN XY: 74246

Gnomad4 AFR AF: 0.0836

Gnomad4 AMR AF: 0.353

Gnomad4 ASJ AF: 0.232

Gnomad4 EAS AF: 0.528

Gnomad4 SAS AF: 0.265

Gnomad4 FIN AF: 0.291

Gnomad4 NFE AF: 0.239

Gnomad4 OTH AF: 0.222

Alfa AF: 0.221 Hom.: 4030

Bravo AF: 0.222

Asia WGS AF: 0.397 AC: 1376 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.6
DANN	Benign	0.86

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3212810; hg19: chr19-51328736; COSMIC: COSV56826948; COSMIC: COSV56826948;