rs1058205

Positions:

• chr19-50860142-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000326003.7(KLK3):​c.*15C>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 0.788 in 1,585,160 control chromosomes in the GnomAD database, including 496,373 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.74 (42412 hom., cov: 32)
  • Exomes 𝑓: 0.79 (453961 hom.)
• Consequence: KLK3 ENST00000326003.7 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.170

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 19-50860142-C-T is Benign according to our data. Variant chr19-50860142-C-T is described in ClinVar as [Benign]. Clinvar id is 1288242.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.819 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLK3	NM_001648.2	c.*15C>T		3_prime_UTR_variant	5/5	ENST00000326003.7	NP_001639.1
KLK3	NM_001030047.1	c.*526C>T		3_prime_UTR_variant	5/5		NP_001025218.1
KLK3	NM_001030048.1	c.*15C>T		3_prime_UTR_variant	5/5		NP_001025219.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLK3	ENST00000326003.7	c.*15C>T		3_prime_UTR_variant	5/5	1	NM_001648.2	ENSP00000314151	P1

Frequencies

GnomAD3 genomes AF: 0.739 AC: 112266 AN: 151962 Hom.: 42398 Cov.: 32

Gnomad AFR AF: 0.597

Gnomad AMI AF: 0.774

Gnomad AMR AF: 0.743

Gnomad ASJ AF: 0.748

Gnomad EAS AF: 0.584

Gnomad SAS AF: 0.629

Gnomad FIN AF: 0.861

Gnomad MID AF: 0.709

Gnomad NFE AF: 0.824

Gnomad OTH AF: 0.731

GnomAD3 exomes AF: 0.751 AC: 185689 AN: 247176 Hom.: 70802 AF XY: 0.753 AC XY: 100486 AN XY: 133496

Gnomad AFR exome AF: 0.597

Gnomad AMR exome AF: 0.715

Gnomad ASJ exome AF: 0.755

Gnomad EAS exome AF: 0.590

Gnomad SAS exome AF: 0.652

Gnomad FIN exome AF: 0.861

Gnomad NFE exome AF: 0.816

Gnomad OTH exome AF: 0.765

GnomAD4 exome AF: 0.793 AC: 1136113 AN: 1433080 Hom.: 453961 Cov.: 24 AF XY: 0.790 AC XY: 563649 AN XY: 713806

Gnomad4 AFR exome AF: 0.593

Gnomad4 AMR exome AF: 0.715

Gnomad4 ASJ exome AF: 0.759

Gnomad4 EAS exome AF: 0.600

Gnomad4 SAS exome AF: 0.650

Gnomad4 FIN exome AF: 0.858

Gnomad4 NFE exome AF: 0.819

Gnomad4 OTH exome AF: 0.772

GnomAD4 genome AF: 0.739 AC: 112326 AN: 152080 Hom.: 42412 Cov.: 32 AF XY: 0.736 AC XY: 54749 AN XY: 74342

Gnomad4 AFR AF: 0.597

Gnomad4 AMR AF: 0.742

Gnomad4 ASJ AF: 0.748

Gnomad4 EAS AF: 0.584

Gnomad4 SAS AF: 0.629

Gnomad4 FIN AF: 0.861

Gnomad4 NFE AF: 0.824

Gnomad4 OTH AF: 0.732

Alfa AF: 0.797 Hom.: 102299

Bravo AF: 0.723

Asia WGS AF: 0.602 AC: 2092 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 29, 2020	This variant is associated with the following publications: (PMID: 25691096) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.44
DANN	Benign	0.49

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: rs1058205; hg19: chr19-51363398;