rs2292186

Variant names:

• chr19-50855138-C-T
• rs2292186
• ENST00000596185.5:n.183C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000596185.5(KLK3):​n.183C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 797,496 control chromosomes in the GnomAD database, including 29,151 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 (4719 hom., cov: 28)
  • Exomes 𝑓: 0.27 (24432 hom.)
• Consequence: KLK3 ENST00000596185.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.446
• Publications: 7 publications found

Genes affected

KLK3 (HGNC:6364): (kallikrein related peptidase 3) 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. The gene is one of the fifteen kallikrein subfamily members located in a cluster on chromosome 19. It encodes a single-chain glycoprotein, a protease which is synthesized in the epithelial cells of the prostate gland, and is present in seminal plasma. It is thought to function normally in the liquefaction of seminal coagulum, presumably by hydrolysis of the high molecular mass seminal vesicle protein. The serum level of this protein, called PSA in the clinical setting, is useful in the diagnosis and monitoring of prostatic carcinoma. Alternate splicing of this gene generates several transcript variants encoding different isoforms. [provided by RefSeq, Dec 2019]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.337 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLK3	NM_001648.2	c.46+137C>T		intron_variant	Intron 1 of 4	ENST00000326003.7	NP_001639.1
KLK3	NM_001030047.1	c.46+137C>T		intron_variant	Intron 1 of 4		NP_001025218.1
KLK3	NM_001030048.1	c.46+137C>T		intron_variant	Intron 1 of 4		NP_001025219.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLK3	ENST00000326003.7	c.46+137C>T		intron_variant	Intron 1 of 4	1	NM_001648.2	ENSP00000314151.1

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34451 AN: 151134 Hom.: 4713 Cov.: 28

Gnomad AFR AF: 0.0878

Gnomad AMI AF: 0.254

Gnomad AMR AF: 0.326

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.351

Gnomad SAS AF: 0.165

Gnomad FIN AF: 0.344

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.269

Gnomad OTH AF: 0.215

GnomAD2 exomes AF: 0.280 AC: 30990 AN: 110526 AF XY: 0.272

Gnomad AFR exome AF: 0.0853

Gnomad AMR exome AF: 0.415

Gnomad ASJ exome AF: 0.238

Gnomad EAS exome AF: 0.355

Gnomad FIN exome AF: 0.338

Gnomad NFE exome AF: 0.268

Gnomad OTH exome AF: 0.257

GnomAD4 exome AF: 0.267 AC: 172389 AN: 646246 Hom.: 24432 Cov.: 8 AF XY: 0.262 AC XY: 88860 AN XY: 339646

African (AFR) AF: 0.0858 AC: 1486 AN: 17318

American (AMR) AF: 0.398 AC: 12286 AN: 30904

Ashkenazi Jewish (ASJ) AF: 0.228 AC: 4037 AN: 17732

East Asian (EAS) AF: 0.347 AC: 11278 AN: 32518

South Asian (SAS) AF: 0.172 AC: 10141 AN: 58842

European-Finnish (FIN) AF: 0.341 AC: 12265 AN: 35984

Middle Eastern (MID) AF: 0.146 AC: 470 AN: 3216

European-Non Finnish (NFE) AF: 0.269 AC: 112254 AN: 416704

Other (OTH) AF: 0.247 AC: 8172 AN: 33028

GnomAD4 genome AF: 0.228 AC: 34469 AN: 151250 Hom.: 4719 Cov.: 28 AF XY: 0.230 AC XY: 16960 AN XY: 73808

African (AFR) AF: 0.0877 AC: 3623 AN: 41328

American (AMR) AF: 0.326 AC: 4949 AN: 15178

Ashkenazi Jewish (ASJ) AF: 0.231 AC: 801 AN: 3466

East Asian (EAS) AF: 0.350 AC: 1776 AN: 5068

South Asian (SAS) AF: 0.166 AC: 791 AN: 4776

European-Finnish (FIN) AF: 0.344 AC: 3590 AN: 10428

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.269 AC: 18191 AN: 67702

Other (OTH) AF: 0.222 AC: 468 AN: 2106

Alfa AF: 0.236 Hom.: 1378

Bravo AF: 0.222

Asia WGS AF: 0.262 AC: 910 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	10
DANN	Benign	0.32
PhyloP100		0.45
PromoterAI		-0.0030	Neutral
Mutation Taster		=100/0	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: rs2292186; hg19: chr19-51358394; COSMIC: COSV58101141; COSMIC: COSV58101141;