chr19-50827676-G-T

Variant names:

• chr19-50827676-G-T
• rs3745522
• NM_017509.4:c.183C>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0960
• Publications: 24 publications found

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

Our verdict: Benign. The variant received -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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLK15	NM_017509.4	MANE Select	c.183C>A	p.Ala61Ala	synonymous	Exon 3 of 6	NP_059979.2
	KLK15	NM_001277081.2		c.180C>A	p.Ala60Ala	synonymous	Exon 3 of 6	NP_001264010.1	Q9H2R5-5
	KLK15	NM_001277082.2		c.180C>A	p.Ala60Ala	synonymous	Exon 3 of 5	NP_001264011.1	M0R0D7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLK15	ENST00000598239.6	TSL:1 MANE Select	c.183C>A	p.Ala61Ala	synonymous	Exon 3 of 6	ENSP00000469315.1	Q9H2R5-1
	KLK15	ENST00000596931.5	TSL:1	c.180C>A	p.Ala60Ala	synonymous	Exon 2 of 4	ENSP00000471164.1	M0R0D7
	KLK15	ENST00000601680.1	TSL:1	n.183C>A		non_coding_transcript_exon	Exon 2 of 4

Frequencies

GnomAD3 genomes AF: 0.229 AC: 34606 AN: 151166 Hom.: 5625 Cov.: 32

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

GnomAD2 exomes AF: 0.302 AC: 75202 AN: 249004 AF XY: 0.294

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 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.: 34 AF XY: 0.267 AC XY: 193975 AN XY: 725694

African (AFR) AF: 0.0643 AC: 2152 AN: 33460

American (AMR) AF: 0.490 AC: 21835 AN: 44548

Ashkenazi Jewish (ASJ) AF: 0.232 AC: 6056 AN: 26092

East Asian (EAS) AF: 0.447 AC: 17723 AN: 39676

South Asian (SAS) AF: 0.269 AC: 23168 AN: 86144

European-Finnish (FIN) AF: 0.299 AC: 15966 AN: 53346

Middle Eastern (MID) AF: 0.187 AC: 1074 AN: 5734

European-Non Finnish (NFE) AF: 0.259 AC: 287358 AN: 1109404

Other (OTH) AF: 0.264 AC: 15906 AN: 60262

GnomAD4 genome AF: 0.229 AC: 34645 AN: 151284 Hom.: 5642 Cov.: 32 AF XY: 0.235 AC XY: 17355 AN XY: 73952

African (AFR) AF: 0.0751 AC: 3111 AN: 41402

American (AMR) AF: 0.366 AC: 5515 AN: 15076

Ashkenazi Jewish (ASJ) AF: 0.242 AC: 835 AN: 3452

East Asian (EAS) AF: 0.511 AC: 2634 AN: 5156

South Asian (SAS) AF: 0.273 AC: 1306 AN: 4778

European-Finnish (FIN) AF: 0.296 AC: 3122 AN: 10532

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.258 AC: 17428 AN: 67594

Other (OTH) AF: 0.232 AC: 486 AN: 2094

Alfa AF: 0.242 Hom.: 7655

Bravo AF: 0.229

Asia WGS AF: 0.398 AC: 1381 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	6.2
DANN	Benign	0.78
PhyloP100		-0.096
Mutation Taster		=97/3	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3745522; hg19: chr19-51330932; COSMIC: COSV56826917; COSMIC: COSV56826917;