Variant 19-50855138-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001648.2(KLK3):c.46+137C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 797,496 control chromosomes in the GnomAD database, including 29,151 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 0.23 ( 4719 hom., cov: 28)

Exomes 𝑓: 0.27 ( 24432 hom. )

Consequence

KLK3
NM_001648.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.446

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.337 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
KLK3	NM_001648.2 linkuse as main transcript	c.46+137C>T	intron_variant	ENST00000326003.7	NP_001639.1
KLK3	NM_001030047.1 linkuse as main transcript	c.46+137C>T	intron_variant		NP_001025218.1
KLK3	NM_001030048.1 linkuse as main transcript	c.46+137C>T	intron_variant		NP_001025219.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLK3	ENST00000326003.7 linkuse as main transcript	c.46+137C>T		intron_variant		1	NM_001648.2	ENSP00000314151	P1	P07288-1

Frequencies

GnomAD3 genomes

AF:

0.228

AC:

34451

AN:

151134

Hom.:

4713

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0878

Gnomad AMI

AF:

0.254

Gnomad AMR

AF:

0.326

Gnomad ASJ

AF:

0.231

Gnomad EAS

AF:

0.351

Gnomad SAS

AF:

0.165

Gnomad FIN

AF:

0.344

Gnomad MID

AF:

0.180

Gnomad NFE

AF:

0.269

Gnomad OTH

AF:

0.215

GnomAD3 exomes

AF:

0.280

AC:

30990

AN:

110526

Hom.:

4727

AF XY:

0.272

AC XY:

15666

AN XY:

57520

show subpopulations

Gnomad AFR exome

AF:

0.0853

Gnomad AMR exome

AF:

0.415

Gnomad ASJ exome

AF:

0.238

Gnomad EAS exome

AF:

0.355

Gnomad SAS exome

AF:

0.173

Gnomad FIN exome

AF:

0.338

Gnomad NFE exome

AF:

0.268

Gnomad OTH exome

AF:

0.257

GnomAD4 exome

AF:

0.267

AC:

172389

AN:

646246

Hom.:

24432

Cov.:

AF XY:

0.262

AC XY:

88860

AN XY:

339646

show subpopulations

Gnomad4 AFR exome

AF:

0.0858

Gnomad4 AMR exome

AF:

0.398

Gnomad4 ASJ exome

AF:

0.228

Gnomad4 EAS exome

AF:

0.347

Gnomad4 SAS exome

AF:

0.172

Gnomad4 FIN exome

AF:

0.341

Gnomad4 NFE exome

AF:

0.269

Gnomad4 OTH exome

AF:

0.247

GnomAD4 genome

AF:

0.228

AC:

34469

AN:

151250

Hom.:

4719

Cov.:

AF XY:

0.230

AC XY:

16960

AN XY:

73808

show subpopulations

Gnomad4 AFR

AF:

0.0877

Gnomad4 AMR

AF:

0.326

Gnomad4 ASJ

AF:

0.231

Gnomad4 EAS

AF:

0.350

Gnomad4 SAS

AF:

0.166

Gnomad4 FIN

AF:

0.344

Gnomad4 NFE

AF:

0.269

Gnomad4 OTH

AF:

0.222

Alfa

AF:

0.246

Hom.:

1288

Bravo

AF:

0.222

Asia WGS

AF:

0.262

AC:

910

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

DANN

Benign

0.32

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over