dbSNP rs1053972: KLK3:n.*103C>T (chr19-50855373-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000596185.5(KLK3):n.*103C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 258,464 control chromosomes in the GnomAD database, including 10,063 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 0.24 ( 5336 hom., cov: 31)

Exomes 𝑓: 0.28 ( 4727 hom. )

Consequence

KLK3
ENST00000596185.5 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.56

Publications

5 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.418 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
KLK3	NM_001648.2 link	c.46+372C>T	intron_variant	Intron 1 of 4	ENST00000326003.7	NP_001639.1	P07288-1Q546G3
KLK3	NM_001030047.1 link	c.46+372C>T	intron_variant	Intron 1 of 4		NP_001025218.1	P07288-2
KLK3	NM_001030048.1 link	c.46+372C>T	intron_variant	Intron 1 of 4		NP_001025219.1	P07288-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLK3	ENST00000326003.7 link	c.46+372C>T		intron_variant	Intron 1 of 4	1	NM_001648.2	ENSP00000314151.1		P07288-1

Frequencies

GnomAD3 genomes

AF:

0.241

AC:

36581

AN:

151886

Hom.:

5329

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0906

Gnomad AMI

AF:

0.258

Gnomad AMR

AF:

0.331

Gnomad ASJ

AF:

0.232

Gnomad EAS

AF:

0.434

Gnomad SAS

AF:

0.171

Gnomad FIN

AF:

0.382

Gnomad MID

AF:

0.184

Gnomad NFE

AF:

0.281

Gnomad OTH

AF:

0.224

GnomAD4 exome

AF:

0.276

AC:

29341

AN:

106460

Hom.:

4727

Cov.:

AF XY:

0.270

AC XY:

14940

AN XY:

55388

show subpopulations

African (AFR)

AF:

0.0813

AC:

280

AN:

3444

American (AMR)

AF:

0.374

AC:

2001

AN:

5354

Ashkenazi Jewish (ASJ)

AF:

0.231

AC:

767

AN:

3324

East Asian (EAS)

AF:

0.454

AC:

2821

AN:

6220

South Asian (SAS)

AF:

0.175

AC:

1882

AN:

10770

European-Finnish (FIN)

AF:

0.376

AC:

1876

AN:

4994

Middle Eastern (MID)

AF:

0.131

AC:

AN:

488

European-Non Finnish (NFE)

AF:

0.275

AC:

18005

AN:

65568

Other (OTH)

AF:

0.261

AC:

1645

AN:

6298

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

1010

2020

3029

4039

5049

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

154

308

462

616

770

<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:

0.241

AC:

36602

AN:

152004

Hom.:

5336

Cov.:

AF XY:

0.245

AC XY:

18170

AN XY:

74306

show subpopulations

African (AFR)

AF:

0.0905

AC:

3753

AN:

41480

American (AMR)

AF:

0.331

AC:

5060

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.232

AC:

806

AN:

3472

East Asian (EAS)

AF:

0.433

AC:

2233

AN:

5154

South Asian (SAS)

AF:

0.171

AC:

825

AN:

4822

European-Finnish (FIN)

AF:

0.382

AC:

4029

AN:

10554

Middle Eastern (MID)

AF:

0.173

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.281

AC:

19122

AN:

67938

Other (OTH)

AF:

0.232

AC:

488

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1329

2658

3988

5317

6646

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

382

764

1146

1528

1910

<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:

0.266

Hom.:

1490

Bravo

AF:

0.232

Asia WGS

AF:

0.295

AC:

1025

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.11

(source)

DANN

Benign

0.53

PhyloP100

-1.6

PromoterAI

-0.0012

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over