rs2659122

Variant names:

• chr19-50859770-C-T
• rs2659122
• ENST00000360617.7:c.*154C>T

Variant summary

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

The ENST00000360617.7(KLK3):​c.*154C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.708 in 1,474,608 control chromosomes in the GnomAD database, including 372,720 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 0.66 (34233 hom., cov: 32)
  • Exomes 𝑓: 0.71 (338487 hom.)
• Consequence: KLK3 ENST00000360617.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0320
• Publications: 19 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 (NFE) allele frequency at 95% confidence interval = 0.73 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLK3	NM_001648.2	c.631-202C>T		intron_variant	Intron 4 of 4	ENST00000326003.7	NP_001639.1
KLK3	NM_001030047.1	c.*154C>T		3_prime_UTR_variant	Exon 5 of 5		NP_001025218.1
KLK3	NM_001030048.1	c.502-202C>T		intron_variant	Intron 4 of 4		NP_001025219.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLK3	ENST00000326003.7	c.631-202C>T		intron_variant	Intron 4 of 4	1	NM_001648.2	ENSP00000314151.1

Frequencies

GnomAD3 genomes AF: 0.664 AC: 100855 AN: 151998 Hom.: 34220 Cov.: 32

Gnomad AFR AF: 0.541

Gnomad AMI AF: 0.596

Gnomad AMR AF: 0.658

Gnomad ASJ AF: 0.618

Gnomad EAS AF: 0.515

Gnomad SAS AF: 0.585

Gnomad FIN AF: 0.822

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.736

Gnomad OTH AF: 0.639

GnomAD4 exome AF: 0.713 AC: 942505 AN: 1322492 Hom.: 338487 Cov.: 42 AF XY: 0.710 AC XY: 456177 AN XY: 642572

African (AFR) AF: 0.538 AC: 16151 AN: 30016

American (AMR) AF: 0.649 AC: 17749 AN: 27328

Ashkenazi Jewish (ASJ) AF: 0.621 AC: 12427 AN: 20018

East Asian (EAS) AF: 0.530 AC: 18877 AN: 35644

South Asian (SAS) AF: 0.602 AC: 40477 AN: 67220

European-Finnish (FIN) AF: 0.816 AC: 35131 AN: 43060

Middle Eastern (MID) AF: 0.594 AC: 2232 AN: 3758

European-Non Finnish (NFE) AF: 0.732 AC: 761956 AN: 1040764

Other (OTH) AF: 0.686 AC: 37505 AN: 54684

GnomAD4 genome AF: 0.663 AC: 100915 AN: 152116 Hom.: 34233 Cov.: 32 AF XY: 0.663 AC XY: 49347 AN XY: 74376

African (AFR) AF: 0.541 AC: 22432 AN: 41472

American (AMR) AF: 0.657 AC: 10049 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.618 AC: 2145 AN: 3470

East Asian (EAS) AF: 0.515 AC: 2654 AN: 5152

South Asian (SAS) AF: 0.585 AC: 2822 AN: 4824

European-Finnish (FIN) AF: 0.822 AC: 8709 AN: 10596

Middle Eastern (MID) AF: 0.595 AC: 175 AN: 294

European-Non Finnish (NFE) AF: 0.736 AC: 50033 AN: 67998

Other (OTH) AF: 0.641 AC: 1354 AN: 2112

Alfa AF: 0.711 Hom.: 68021

Bravo AF: 0.643

Asia WGS AF: 0.545 AC: 1896 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	3.8
DANN	Benign	0.45
PhyloP100		-0.032
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: rs2659122; hg19: chr19-51363026;