Variant rs61752561 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_001648.2(KLK3):c.304G>A(p.Asp102Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0343 in 1,614,032 control chromosomes in the GnomAD database, including 1,191 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.025 ( 67 hom., cov: 31)

Exomes 𝑓: 0.035 ( 1124 hom. )

Consequence

KLK3
NM_001648.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.104

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003840983).

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0247 (3759/152180) while in subpopulation NFE AF= 0.0418 (2843/68012). AF 95% confidence interval is 0.0405. There are 67 homozygotes in gnomad4. There are 1754 alleles in male gnomad4 subpopulation. This position pass quality control queck.

BS2

High Homozygotes in GnomAd at 67 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
KLK3	NM_001648.2 linkuse as main transcript	c.304G>A	p.Asp102Asn	missense_variant	3/5	ENST00000326003.7
KLK3	NM_001030047.1 linkuse as main transcript	c.304G>A	p.Asp102Asn	missense_variant	3/5
KLK3	NM_001030048.1 linkuse as main transcript	c.207-32G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KLK3	ENST00000326003.7 linkuse as main transcript	c.304G>A	p.Asp102Asn	missense_variant	3/5	1	NM_001648.2	P1	P07288-1

Frequencies

GnomAD3 genomes

AF:

0.0247

AC:

3758

AN:

152062

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00700

Gnomad AMI

AF:

0.0121

Gnomad AMR

AF:

0.00990

Gnomad ASJ

AF:

0.00980

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00894

Gnomad FIN

AF:

0.0331

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0418

Gnomad OTH

AF:

0.0158

GnomAD3 exomes

AF:

0.0239

AC:

5995

AN:

251316

Hom.:

112

AF XY:

0.0245

AC XY:

3326

AN XY:

135848

show subpopulations

Gnomad AFR exome

AF:

0.00720

Gnomad AMR exome

AF:

0.00616

Gnomad ASJ exome

AF:

0.0100

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0112

Gnomad FIN exome

AF:

0.0322

Gnomad NFE exome

AF:

0.0388

Gnomad OTH exome

AF:

0.0192

GnomAD4 exome

AF:

0.0353

AC:

51618

AN:

1461852

Hom.:

1124

Cov.:

AF XY:

0.0347

AC XY:

25243

AN XY:

727224

show subpopulations

Gnomad4 AFR exome

AF:

0.00568

Gnomad4 AMR exome

AF:

0.00673

Gnomad4 ASJ exome

AF:

0.0118

Gnomad4 EAS exome

AF:

0.000151

Gnomad4 SAS exome

AF:

0.0102

Gnomad4 FIN exome

AF:

0.0341

Gnomad4 NFE exome

AF:

0.0418

Gnomad4 OTH exome

AF:

0.0267

GnomAD4 genome

AF:

0.0247

AC:

3759

AN:

152180

Hom.:

Cov.:

AF XY:

0.0236

AC XY:

1754

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.00698

Gnomad4 AMR

AF:

0.00988

Gnomad4 ASJ

AF:

0.00980

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00916

Gnomad4 FIN

AF:

0.0331

Gnomad4 NFE

AF:

0.0418

Gnomad4 OTH

AF:

0.0156

Alfa

AF:

0.0353

Hom.:

187

Bravo

AF:

0.0218

ESP6500AA

AF:

0.00953

AC:

ESP6500EA

AF:

0.0391

AC:

336

ExAC

AF:

0.0259

AC:

3148

Asia WGS

AF:

0.00404

AC:

AN:

3478

EpiCase

AF:

0.0349

EpiControl

AF:

0.0345

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.58

Cadd

Benign

0.11

Dann

Benign

0.21

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.00068

LIST_S2

Benign

0.64

T;T;T;T;T;T

MetaRNN

Benign

0.0038

T;T;T;T;T;T

MetaSVM

Benign

-0.90

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.30

Sift4G

Benign

1.0

T;T;T;T;T;T

Polyphen

0.0

.;.;B;.;.;.

Vest4

0.081, 0.12, 0.050

MPC

0.075

ClinPred

0.00048

GERP RS

-1.6

Varity_R

0.13

gMVP

0.19

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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