chr19-50856241-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_001648.2(KLK3):c.48T>C(p.Gly16Gly) 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

Publications

20 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001648.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
KLK3	NM_001648.2	MANE Select	c.48T>C	p.Gly16Gly	splice_region synonymous	Exon 2 of 5	NP_001639.1
KLK3	NM_001030047.1		c.48T>C	p.Gly16Gly	splice_region synonymous	Exon 2 of 5	NP_001025218.1
KLK3	NM_001030048.1		c.48T>C	p.Gly16Gly	splice_region synonymous	Exon 2 of 5	NP_001025219.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
KLK3	ENST00000326003.7	TSL:1 MANE Select	c.48T>C	p.Gly16Gly	splice_region synonymous	Exon 2 of 5	ENSP00000314151.1
KLK3	ENST00000360617.7	TSL:1	c.48T>C	p.Gly16Gly	splice_region synonymous	Exon 2 of 5	ENSP00000353829.2
KLK3	ENST00000593997.5	TSL:1	c.48T>C	p.Gly16Gly	splice_region synonymous	Exon 2 of 4	ENSP00000472907.1

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

GnomAD2 exomes

AF:

0.403

AC:

100569

AN:

249588

AF XY:

0.391

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 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

African (AFR)

AF:

0.217

AC:

7221

AN:

33326

American (AMR)

AF:

0.511

AC:

22814

AN:

44622

Ashkenazi Jewish (ASJ)

AF:

0.387

AC:

10055

AN:

25988

East Asian (EAS)

AF:

0.513

AC:

20323

AN:

39652

South Asian (SAS)

AF:

0.238

AC:

20419

AN:

85952

European-Finnish (FIN)

AF:

0.462

AC:

24603

AN:

53294

Middle Eastern (MID)

AF:

0.297

AC:

1351

AN:

4546

European-Non Finnish (NFE)

AF:

0.420

AC:

464826

AN:

1107374

Other (OTH)

AF:

0.399

AC:

23955

AN:

60090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.437

Heterozygous variant carriers

16132

32264

48397

64529

80661

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14146

28292

42438

56584

70730

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.370

AC:

56128

AN:

151814

Hom.:

11196

Cov.:

AF XY:

0.370

AC XY:

27416

AN XY:

74196

show subpopulations

African (AFR)

AF:

0.228

AC:

9444

AN:

41456

American (AMR)

AF:

0.456

AC:

6958

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.380

AC:

1317

AN:

3462

East Asian (EAS)

AF:

0.506

AC:

2608

AN:

5152

South Asian (SAS)

AF:

0.226

AC:

1085

AN:

4800

European-Finnish (FIN)

AF:

0.460

AC:

4847

AN:

10530

Middle Eastern (MID)

AF:

0.310

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.421

AC:

28575

AN:

67834

Other (OTH)

AF:

0.379

AC:

802

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1759

3519

5278

7038

8797

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

536

1072

1608

2144

2680

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.395

Hom.:

11012

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

Oct 18, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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 v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.92

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.57

(source)

DANN

Benign

0.25

FATHMM_MKL

Benign

0.040

PhyloP100

-0.53

GERP RS

-1.4

Mutation Taster

=95/5

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over