Variant 19-50855215-C-G 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+214C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.447 in 568,230 control chromosomes in the GnomAD database, including 59,414 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 0.46 ( 16962 hom., cov: 29)

Exomes 𝑓: 0.44 ( 42452 hom. )

Consequence

KLK3
NM_001648.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.316

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 (AFR) allele frequency at 95% confidence interval = 0.521 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
KLK3	NM_001648.2 linkuse as main transcript	c.46+214C>G	intron_variant	ENST00000326003.7	NP_001639.1
KLK3	NM_001030047.1 linkuse as main transcript	c.46+214C>G	intron_variant		NP_001025218.1
KLK3	NM_001030048.1 linkuse as main transcript	c.46+214C>G	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+214C>G		intron_variant		1	NM_001648.2	ENSP00000314151	P1	P07288-1

Frequencies

GnomAD3 genomes

AF:

0.464

AC:

70424

AN:

151668

Hom.:

16955

Cov.:

show subpopulations

Gnomad AFR

AF:

0.527

Gnomad AMI

AF:

0.345

Gnomad AMR

AF:

0.355

Gnomad ASJ

AF:

0.428

Gnomad EAS

AF:

0.161

Gnomad SAS

AF:

0.386

Gnomad FIN

AF:

0.503

Gnomad MID

AF:

0.443

Gnomad NFE

AF:

0.478

Gnomad OTH

AF:

0.449

GnomAD3 exomes

AF:

0.388

AC:

17806

AN:

45858

Hom.:

3857

AF XY:

0.388

AC XY:

8881

AN XY:

22902

show subpopulations

Gnomad AFR exome

AF:

0.515

Gnomad AMR exome

AF:

0.296

Gnomad ASJ exome

AF:

0.391

Gnomad EAS exome

AF:

0.153

Gnomad SAS exome

AF:

0.405

Gnomad FIN exome

AF:

0.515

Gnomad NFE exome

AF:

0.478

Gnomad OTH exome

AF:

0.418

GnomAD4 exome

AF:

0.440

AC:

183280

AN:

416446

Hom.:

42452

Cov.:

AF XY:

0.439

AC XY:

96083

AN XY:

218950

show subpopulations

Gnomad4 AFR exome

AF:

0.521

Gnomad4 AMR exome

AF:

0.295

Gnomad4 ASJ exome

AF:

0.432

Gnomad4 EAS exome

AF:

0.188

Gnomad4 SAS exome

AF:

0.399

Gnomad4 FIN exome

AF:

0.501

Gnomad4 NFE exome

AF:

0.475

Gnomad4 OTH exome

AF:

0.446

GnomAD4 genome

AF:

0.464

AC:

70459

AN:

151784

Hom.:

16962

Cov.:

AF XY:

0.461

AC XY:

34227

AN XY:

74176

show subpopulations

Gnomad4 AFR

AF:

0.527

Gnomad4 AMR

AF:

0.354

Gnomad4 ASJ

AF:

0.428

Gnomad4 EAS

AF:

0.162

Gnomad4 SAS

AF:

0.386

Gnomad4 FIN

AF:

0.503

Gnomad4 NFE

AF:

0.478

Gnomad4 OTH

AF:

0.444

Alfa

AF:

0.361

Hom.:

1245

Bravo

AF:

0.453

Asia WGS

AF:

0.281

AC:

978

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

6.0

DANN

Benign

0.36

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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