ENST00000422986.6:n.*720G>A – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000422986.6(KLK3):n.*720G>A 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 0.302 in 295,536 control chromosomes in the GnomAD database, including 15,238 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 0.29 ( 7366 hom., cov: 32)

Exomes 𝑓: 0.32 ( 7872 hom. )

Consequence

KLK3
ENST00000422986.6 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.711

Publications

16 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=-0.91).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.415 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
KLK3	NM_001648.2 link	c.*278G>A	3_prime_UTR_variant	Exon 5 of 5	ENST00000326003.7	NP_001639.1	P07288-1Q546G3
KLK3	NM_001030047.1 link	c.*789G>A	3_prime_UTR_variant	Exon 5 of 5		NP_001025218.1	P07288-2
KLK3	NM_001030048.1 link	c.*278G>A	3_prime_UTR_variant	Exon 5 of 5		NP_001025219.1	P07288-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLK3	ENST00000326003.7 link	c.*278G>A		3_prime_UTR_variant	Exon 5 of 5	1	NM_001648.2	ENSP00000314151.1		P07288-1

Frequencies

GnomAD3 genomes

AF:

0.287

AC:

43614

AN:

151858

Hom.:

7362

Cov.:

show subpopulations

Gnomad AFR

AF:

0.129

Gnomad AMI

AF:

0.253

Gnomad AMR

AF:

0.378

Gnomad ASJ

AF:

0.250

Gnomad EAS

AF:

0.431

Gnomad SAS

AF:

0.184

Gnomad FIN

AF:

0.459

Gnomad MID

AF:

0.215

Gnomad NFE

AF:

0.336

Gnomad OTH

AF:

0.272

GnomAD4 exome

AF:

0.318

AC:

45599

AN:

143560

Hom.:

7872

Cov.:

AF XY:

0.313

AC XY:

23124

AN XY:

73856

show subpopulations

African (AFR)

AF:

0.115

AC:

613

AN:

5326

American (AMR)

AF:

0.392

AC:

2324

AN:

5922

Ashkenazi Jewish (ASJ)

AF:

0.229

AC:

1175

AN:

5134

East Asian (EAS)

AF:

0.427

AC:

4399

AN:

10306

South Asian (SAS)

AF:

0.165

AC:

1386

AN:

8384

European-Finnish (FIN)

AF:

0.450

AC:

4077

AN:

9066

Middle Eastern (MID)

AF:

0.173

AC:

123

AN:

710

European-Non Finnish (NFE)

AF:

0.322

AC:

28786

AN:

89522

Other (OTH)

AF:

0.296

AC:

2716

AN:

9190

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1469

2937

4406

5874

7343

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

186

372

558

744

930

<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:

0.287

AC:

43634

AN:

151976

Hom.:

7366

Cov.:

AF XY:

0.291

AC XY:

21582

AN XY:

74288

show subpopulations

African (AFR)

AF:

0.129

AC:

5335

AN:

41460

American (AMR)

AF:

0.378

AC:

5780

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.250

AC:

867

AN:

3464

East Asian (EAS)

AF:

0.430

AC:

2222

AN:

5168

South Asian (SAS)

AF:

0.184

AC:

884

AN:

4808

European-Finnish (FIN)

AF:

0.459

AC:

4844

AN:

10550

Middle Eastern (MID)

AF:

0.204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.336

AC:

22825

AN:

67928

Other (OTH)

AF:

0.278

AC:

587

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1492

2984

4477

5969

7461

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

442

884

1326

1768

2210

<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:

0.310

Hom.:

12425

Bravo

AF:

0.274

Asia WGS

AF:

0.309

AC:

1073

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.30

(source)

DANN

Benign

0.55

PhyloP100

-0.71

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