rs3212853

Positions:

• chr19-50825538-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_017509.4(KLK15):​c.*258G>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 0.0262 in 349,582 control chromosomes in the GnomAD database, including 173 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 0.025 (64 hom., cov: 32)
  • Exomes 𝑓: 0.027 (109 hom.)
• Consequence: KLK15 NM_017509.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.128

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0246 (3742/152228) while in subpopulation NFE AF= 0.0368 (2505/68008). AF 95% confidence interval is 0.0356. There are 64 homozygotes in gnomad4. There are 1734 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 64 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KLK15	NM_017509.4	c.*258G>A		3_prime_UTR_variant	6/6	ENST00000598239.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KLK15	ENST00000598239.6	c.*258G>A		3_prime_UTR_variant	6/6	1	NM_017509.4	P4

Frequencies

GnomAD3 genomes AF: 0.0246 AC: 3741 AN: 152112 Hom.: 64 Cov.: 32

Gnomad AFR AF: 0.00669

Gnomad AMI AF: 0.0647

Gnomad AMR AF: 0.0353

Gnomad ASJ AF: 0.0349

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00560

Gnomad FIN AF: 0.0127

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0368

Gnomad OTH AF: 0.0311

GnomAD4 exome AF: 0.0274 AC: 5404 AN: 197354 Hom.: 109 Cov.: 2 AF XY: 0.0267 AC XY: 2695 AN XY: 101072

Gnomad4 AFR exome AF: 0.00684

Gnomad4 AMR exome AF: 0.0278

Gnomad4 ASJ exome AF: 0.0322

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00525

Gnomad4 FIN exome AF: 0.0187

Gnomad4 NFE exome AF: 0.0345

Gnomad4 OTH exome AF: 0.0286

GnomAD4 genome AF: 0.0246 AC: 3742 AN: 152228 Hom.: 64 Cov.: 32 AF XY: 0.0233 AC XY: 1734 AN XY: 74424

Gnomad4 AFR AF: 0.00667

Gnomad4 AMR AF: 0.0353

Gnomad4 ASJ AF: 0.0349

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00581

Gnomad4 FIN AF: 0.0127

Gnomad4 NFE AF: 0.0368

Gnomad4 OTH AF: 0.0308

Alfa AF: 0.0359 Hom.: 98

Bravo AF: 0.0257

Asia WGS AF: 0.00346 AC: 12 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.3
DANN	Benign	0.79

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3212853; hg19: chr19-51328794;