Variant 19-50856241-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_001648.2(KLK3):c.48T>C(p.Gly16=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.406 in 1,606,658 control chromosomes in the GnomAD database, including 136,964 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.37 ( 11196 hom., cov: 31)

Exomes 𝑓: 0.41 ( 125768 hom. )

Consequence

KLK3
NM_001648.2 splice_region, synonymous

Scores

Splicing: ADA: 0.0005339

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.529

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_addAF=-0.922523).

BP6

Variant 19-50856241-T-C is Benign according to our data. Variant chr19-50856241-T-C is described in ClinVar as [Benign]. Clinvar id is 3059788.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.49 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
KLK3	NM_001648.2 linkuse as main transcript	c.48T>C	p.Gly16=	splice_region_variant, synonymous_variant	2/5	ENST00000326003.7	NP_001639.1
KLK3	NM_001030047.1 linkuse as main transcript	c.48T>C	p.Gly16=	splice_region_variant, synonymous_variant	2/5		NP_001025218.1
KLK3	NM_001030048.1 linkuse as main transcript	c.48T>C	p.Gly16=	splice_region_variant, synonymous_variant	2/5		NP_001025219.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLK3	ENST00000326003.7 linkuse as main transcript	c.48T>C	p.Gly16=	splice_region_variant, synonymous_variant	2/5	1	NM_001648.2	ENSP00000314151	P1	P07288-1

Frequencies

GnomAD3 genomes

AF:

0.370

AC:

56103

AN:

151696

Hom.:

11191

Cov.:

show subpopulations

Gnomad AFR

AF:

0.228

Gnomad AMI

AF:

0.444

Gnomad AMR

AF:

0.456

Gnomad ASJ

AF:

0.380

Gnomad EAS

AF:

0.507

Gnomad SAS

AF:

0.226

Gnomad FIN

AF:

0.460

Gnomad MID

AF:

0.326

Gnomad NFE

AF:

0.421

Gnomad OTH

AF:

0.373

GnomAD3 exomes

AF:

0.403

AC:

100569

AN:

249588

Hom.:

21569

AF XY:

0.391

AC XY:

52809

AN XY:

134912

show subpopulations

Gnomad AFR exome

AF:

0.227

Gnomad AMR exome

AF:

0.523

Gnomad ASJ exome

AF:

0.384

Gnomad EAS exome

AF:

0.515

Gnomad SAS exome

AF:

0.233

Gnomad FIN exome

AF:

0.457

Gnomad NFE exome

AF:

0.411

Gnomad OTH exome

AF:

0.399

GnomAD4 exome

AF:

0.409

AC:

595567

AN:

1454844

Hom.:

125768

Cov.:

AF XY:

0.404

AC XY:

292654

AN XY:

724004

show subpopulations

Gnomad4 AFR exome

AF:

0.217

Gnomad4 AMR exome

AF:

0.511

Gnomad4 ASJ exome

AF:

0.387

Gnomad4 EAS exome

AF:

0.513

Gnomad4 SAS exome

AF:

0.238

Gnomad4 FIN exome

AF:

0.462

Gnomad4 NFE exome

AF:

0.420

Gnomad4 OTH exome

AF:

0.399

GnomAD4 genome

AF:

0.370

AC:

56128

AN:

151814

Hom.:

11196

Cov.:

AF XY:

0.370

AC XY:

27416

AN XY:

74196

show subpopulations

Gnomad4 AFR

AF:

0.228

Gnomad4 AMR

AF:

0.456

Gnomad4 ASJ

AF:

0.380

Gnomad4 EAS

AF:

0.506

Gnomad4 SAS

AF:

0.226

Gnomad4 FIN

AF:

0.460

Gnomad4 NFE

AF:

0.421

Gnomad4 OTH

AF:

0.379

Alfa

AF:

0.395

Hom.:

10865

Bravo

AF:

0.368

TwinsUK

AF:

0.417

AC:

1546

ALSPAC

AF:

0.417

AC:

1607

ESP6500AA

AF:

0.242

AC:

1066

ESP6500EA

AF:

0.417

AC:

3589

ExAC

AF:

0.393

AC:

47683

Asia WGS

AF:

0.363

AC:

1264

AN:

3478

EpiCase

AF:

0.406

EpiControl

AF:

0.406

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

Oct 18, 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_addAF

Benign

-0.92

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.57

DANN

Benign

0.25

FATHMM_MKL

Benign

0.040

MutationTaster

Benign

1.0e-37

P;P;P;P

GERP RS

-1.4

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00053

dbscSNV1_RF

Benign

0.056

SpliceAI score (max)

0.26

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.26

Position offset: -1

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