dbSNP rs1061477: KLK3:c.206+441T>C (chr19-50856840-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001648.2(KLK3):c.206+441T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.418 in 159,114 control chromosomes in the GnomAD database, including 15,160 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 0.42 ( 14487 hom., cov: 28)

Exomes 𝑓: 0.37 ( 673 hom. )

Consequence

KLK3
NM_001648.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.175

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=-0.97).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.494 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
KLK3	NM_001648.2 link	c.206+441T>C	intron_variant	Intron 2 of 4	ENST00000326003.7	NP_001639.1	P07288-1Q546G3
KLK3	NM_001030047.1 link	c.206+441T>C	intron_variant	Intron 2 of 4		NP_001025218.1	P07288-2
KLK3	NM_001030048.1 link	c.206+441T>C	intron_variant	Intron 2 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.206+441T>C		intron_variant	Intron 2 of 4	1	NM_001648.2	ENSP00000314151.1		P07288-1

Frequencies

GnomAD3 genomes

AF:

0.421

AC:

63509

AN:

150864

Hom.:

14483

Cov.:

show subpopulations

Gnomad AFR

AF:

0.243

Gnomad AMI

AF:

0.630

Gnomad AMR

AF:

0.489

Gnomad ASJ

AF:

0.476

Gnomad EAS

AF:

0.503

Gnomad SAS

AF:

0.280

Gnomad FIN

AF:

0.513

Gnomad MID

AF:

0.388

Gnomad NFE

AF:

0.498

Gnomad OTH

AF:

0.424

GnomAD4 exome

AF:

0.368

AC:

2994

AN:

8130

Hom.:

673

AF XY:

0.366

AC XY:

1630

AN XY:

4450

show subpopulations

African (AFR)

AF:

0.226

AC:

AN:

124

American (AMR)

AF:

0.428

AC:

260

AN:

608

Ashkenazi Jewish (ASJ)

AF:

0.291

AC:

AN:

182

East Asian (EAS)

AF:

0.407

AC:

AN:

140

South Asian (SAS)

AF:

0.173

AC:

134

AN:

774

European-Finnish (FIN)

AF:

0.395

AC:

AN:

220

Middle Eastern (MID)

AF:

0.423

AC:

AN:

European-Non Finnish (NFE)

AF:

0.394

AC:

2200

AN:

5584

Other (OTH)

AF:

0.347

AC:

164

AN:

472

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

160

239

319

399

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.421

AC:

63536

AN:

150984

Hom.:

14487

Cov.:

AF XY:

0.418

AC XY:

30810

AN XY:

73710

show subpopulations

African (AFR)

AF:

0.242

AC:

9982

AN:

41198

American (AMR)

AF:

0.489

AC:

7420

AN:

15178

Ashkenazi Jewish (ASJ)

AF:

0.476

AC:

1649

AN:

3464

East Asian (EAS)

AF:

0.503

AC:

2540

AN:

5054

South Asian (SAS)

AF:

0.280

AC:

1338

AN:

4780

European-Finnish (FIN)

AF:

0.513

AC:

5350

AN:

10438

Middle Eastern (MID)

AF:

0.376

AC:

109

AN:

290

European-Non Finnish (NFE)

AF:

0.498

AC:

33696

AN:

67608

Other (OTH)

AF:

0.428

AC:

893

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

1686

3371

5057

6742

8428

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

582

1164

1746

2328

2910

<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:

0.478

Hom.:

14289

Bravo

AF:

0.418

Asia WGS

AF:

0.373

AC:

1299

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

3.4

(source)

DANN

Benign

0.28

PhyloP100

-0.17

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