Variant chr19-50858059-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_001648.2(KLK3):c.237C>T(p.Ser79Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 1,613,068 control chromosomes in the GnomAD database, including 11,850 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.11 ( 868 hom., cov: 31)

Exomes 𝑓: 0.12 ( 10982 hom. )

Consequence

KLK3
NM_001648.2 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.42

Variant links:

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 links:

KLK3 (HGNC:):

KLK3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP6

Variant 19-50858059-C-T is Benign according to our data. Variant chr19-50858059-C-T is described in ClinVar as [Benign]. Clinvar id is 3057076.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=2.42 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.125 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLK3	NM_001648.2 linkuse as main transcript	c.237C>T	p.Ser79Ser	synonymous_variant	3/5	ENST00000326003.7	NP_001639.1	P07288-1Q546G3
KLK3	NM_001030047.1 linkuse as main transcript	c.237C>T	p.Ser79Ser	synonymous_variant	3/5		NP_001025218.1	P07288-2
KLK3	NM_001030048.1 linkuse as main transcript	c.207-99C>T		intron_variant			NP_001025219.1	P07288-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLK3	ENST00000326003.7 linkuse as main transcript	c.237C>T	p.Ser79Ser	synonymous_variant	3/5	1	NM_001648.2	ENSP00000314151.1		P07288-1

Frequencies

GnomAD3 genomes

AF:

0.106

AC:

16058

AN:

152088

Hom.:

869

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0789

Gnomad AMI

AF:

0.179

Gnomad AMR

AF:

0.103

Gnomad ASJ

AF:

0.191

Gnomad EAS

AF:

0.0717

Gnomad SAS

AF:

0.0841

Gnomad FIN

AF:

0.0634

Gnomad MID

AF:

0.146

Gnomad NFE

AF:

0.127

Gnomad OTH

AF:

0.127

GnomAD3 exomes

AF:

0.106

AC:

26495

AN:

250016

Hom.:

1535

AF XY:

0.108

AC XY:

14582

AN XY:

135150

show subpopulations

Gnomad AFR exome

AF:

0.0778

Gnomad AMR exome

AF:

0.0844

Gnomad ASJ exome

AF:

0.193

Gnomad EAS exome

AF:

0.0748

Gnomad SAS exome

AF:

0.0852

Gnomad FIN exome

AF:

0.0657

Gnomad NFE exome

AF:

0.126

Gnomad OTH exome

AF:

0.128

GnomAD4 exome

AF:

0.120

AC:

175196

AN:

1460862

Hom.:

10982

Cov.:

AF XY:

0.120

AC XY:

87060

AN XY:

726750

show subpopulations

Gnomad4 AFR exome

AF:

0.0777

Gnomad4 AMR exome

AF:

0.0840

Gnomad4 ASJ exome

AF:

0.196

Gnomad4 EAS exome

AF:

0.0700

Gnomad4 SAS exome

AF:

0.0866

Gnomad4 FIN exome

AF:

0.0666

Gnomad4 NFE exome

AF:

0.127

Gnomad4 OTH exome

AF:

0.122

GnomAD4 genome

AF:

0.106

AC:

16061

AN:

152206

Hom.:

868

Cov.:

AF XY:

0.103

AC XY:

7638

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.0787

Gnomad4 AMR

AF:

0.103

Gnomad4 ASJ

AF:

0.191

Gnomad4 EAS

AF:

0.0718

Gnomad4 SAS

AF:

0.0850

Gnomad4 FIN

AF:

0.0634

Gnomad4 NFE

AF:

0.127

Gnomad4 OTH

AF:

0.126

Alfa

AF:

0.123

Hom.:

1836

Bravo

AF:

0.108

Asia WGS

AF:

0.0690

AC:

241

AN:

3478

EpiCase

AF:

0.133

EpiControl

AF:

0.138

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

KLK3-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 12, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

4.7

DANN

Benign

0.46

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over