rs34750956

Positions:

• chr19-50858740-C-T

Variant summary

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

The ENST00000593997.5(KLK3):​c.*91C>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 0.109 in 806,578 control chromosomes in the GnomAD database, including 5,186 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 0.10 (831 hom., cov: 32)
  • Exomes 𝑓: 0.11 (4355 hom.)
• Consequence: KLK3 ENST00000593997.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.798

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.119 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KLK3	NM_001648.2	c.630+145C>T		intron_variant		ENST00000326003.7
KLK3	NM_001030047.1	c.630+145C>T		intron_variant
KLK3	NM_001030048.1	c.501+145C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KLK3	ENST00000326003.7	c.630+145C>T		intron_variant		1	NM_001648.2	P1

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15535 AN: 152080 Hom.: 832 Cov.: 32

Gnomad AFR AF: 0.0770

Gnomad AMI AF: 0.178

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.194

Gnomad EAS AF: 0.0705

Gnomad SAS AF: 0.0847

Gnomad FIN AF: 0.0546

Gnomad MID AF: 0.150

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.124

GnomAD4 exome AF: 0.110 AC: 72169 AN: 654378 Hom.: 4355 Cov.: 9 AF XY: 0.110 AC XY: 37417 AN XY: 338650

Gnomad4 AFR exome AF: 0.0752

Gnomad4 AMR exome AF: 0.0878

Gnomad4 ASJ exome AF: 0.198

Gnomad4 EAS exome AF: 0.0681

Gnomad4 SAS exome AF: 0.0850

Gnomad4 FIN exome AF: 0.0586

Gnomad4 NFE exome AF: 0.119

Gnomad4 OTH exome AF: 0.118

GnomAD4 genome AF: 0.102 AC: 15539 AN: 152200 Hom.: 831 Cov.: 32 AF XY: 0.0991 AC XY: 7375 AN XY: 74412

Gnomad4 AFR AF: 0.0769

Gnomad4 AMR AF: 0.105

Gnomad4 ASJ AF: 0.194

Gnomad4 EAS AF: 0.0707

Gnomad4 SAS AF: 0.0859

Gnomad4 FIN AF: 0.0546

Gnomad4 NFE AF: 0.121

Gnomad4 OTH AF: 0.123

Alfa AF: 0.105 Hom.: 188

Bravo AF: 0.106

Asia WGS AF: 0.0700 AC: 243 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.5
DANN	Benign	0.49

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs34750956; hg19: chr19-51361996;