Variant 19-50860142-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001648.2(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
NM_001648.2 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.170

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:

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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=-0.91).

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_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.819 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
KLK3	NM_001648.2 linkuse as main transcript	c.*15C>T	3_prime_UTR_variant	5/5	ENST00000326003.7
KLK3	NM_001030047.1 linkuse as main transcript	c.*526C>T	3_prime_UTR_variant	5/5
KLK3	NM_001030048.1 linkuse as main transcript	c.*15C>T	3_prime_UTR_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KLK3	ENST00000326003.7 linkuse as main transcript	c.*15C>T		3_prime_UTR_variant	5/5	1	NM_001648.2	P1	P07288-1

Frequencies

GnomAD3 genomes

AF:

0.739

AC:

112266

AN:

151962

Hom.:

42398

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.790

AC XY:

563649

AN XY:

713806

show subpopulations

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.:

AF XY:

0.736

AC XY:

54749

AN XY:

74342

show subpopulations

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:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

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

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