rs2659122

Positions:

• chr19-50859770-C-T

Variant summary

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

The NM_001030047.1(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 NM_001030047.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0320

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]

KLK3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
KLK3	NM_001648.2	c.631-202C>T		intron_variant		ENST00000326003.7	NP_001639.1
KLK3	NM_001030047.1	c.*154C>T		3_prime_UTR_variant	5/5		NP_001025218.1
KLK3	NM_001030048.1	c.502-202C>T		intron_variant			NP_001025219.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLK3	ENST00000326003.7	c.631-202C>T		intron_variant		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

Gnomad4 AFR exome AF: 0.538

Gnomad4 AMR exome AF: 0.649

Gnomad4 ASJ exome AF: 0.621

Gnomad4 EAS exome AF: 0.530

Gnomad4 SAS exome AF: 0.602

Gnomad4 FIN exome AF: 0.816

Gnomad4 NFE exome AF: 0.732

Gnomad4 OTH exome AF: 0.686

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

Gnomad4 AFR AF: 0.541

Gnomad4 AMR AF: 0.657

Gnomad4 ASJ AF: 0.618

Gnomad4 EAS AF: 0.515

Gnomad4 SAS AF: 0.585

Gnomad4 FIN AF: 0.822

Gnomad4 NFE AF: 0.736

Gnomad4 OTH AF: 0.641

Alfa AF: 0.711 Hom.: 45564

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs2659122; hg19: chr19-51363026;