Variant rs266875 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000593997.5(KLK3):c.*32G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.558 in 1,496,438 control chromosomes in the GnomAD database, including 236,436 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 0.60 ( 27928 hom., cov: 31)

Exomes 𝑓: 0.55 ( 208508 hom. )

Consequence

KLK3
ENST00000593997.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.561

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:

KLK3 (HGNC:):

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 (BayesDel_noAF=-1.0).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.743 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
KLK3	NM_001648.2 linkuse as main transcript	c.630+86G>A	intron_variant	ENST00000326003.7	NP_001639.1	P07288-1Q546G3
KLK3	NM_001030047.1 linkuse as main transcript	c.630+86G>A	intron_variant		NP_001025218.1	P07288-2
KLK3	NM_001030048.1 linkuse as main transcript	c.501+86G>A	intron_variant		NP_001025219.1	P07288-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLK3	ENST00000326003.7 linkuse as main transcript	c.630+86G>A		intron_variant		1	NM_001648.2	ENSP00000314151.1		P07288-1

Frequencies

GnomAD3 genomes

AF:

0.596

AC:

90478

AN:

151892

Hom.:

27895

Cov.:

show subpopulations

Gnomad AFR

AF:

0.750

Gnomad AMI

AF:

0.569

Gnomad AMR

AF:

0.513

Gnomad ASJ

AF:

0.531

Gnomad EAS

AF:

0.499

Gnomad SAS

AF:

0.730

Gnomad FIN

AF:

0.486

Gnomad MID

AF:

0.623

Gnomad NFE

AF:

0.538

Gnomad OTH

AF:

0.597

GnomAD3 exomes

AF:

0.565

AC:

120919

AN:

214090

Hom.:

34715

AF XY:

0.574

AC XY:

66209

AN XY:

115412

show subpopulations

Gnomad AFR exome

AF:

0.752

Gnomad AMR exome

AF:

0.464

Gnomad ASJ exome

AF:

0.546

Gnomad EAS exome

AF:

0.494

Gnomad SAS exome

AF:

0.729

Gnomad FIN exome

AF:

0.497

Gnomad NFE exome

AF:

0.553

Gnomad OTH exome

AF:

0.562

GnomAD4 exome

AF:

0.553

AC:

743853

AN:

1344428

Hom.:

208508

Cov.:

AF XY:

0.558

AC XY:

372585

AN XY:

667972

show subpopulations

Gnomad4 AFR exome

AF:

0.762

Gnomad4 AMR exome

AF:

0.472

Gnomad4 ASJ exome

AF:

0.534

Gnomad4 EAS exome

AF:

0.492

Gnomad4 SAS exome

AF:

0.718

Gnomad4 FIN exome

AF:

0.492

Gnomad4 NFE exome

AF:

0.542

Gnomad4 OTH exome

AF:

0.563

GnomAD4 genome

AF:

0.596

AC:

90563

AN:

152010

Hom.:

27928

Cov.:

AF XY:

0.596

AC XY:

44281

AN XY:

74286

show subpopulations

Gnomad4 AFR

AF:

0.750

Gnomad4 AMR

AF:

0.513

Gnomad4 ASJ

AF:

0.531

Gnomad4 EAS

AF:

0.500

Gnomad4 SAS

AF:

0.730

Gnomad4 FIN

AF:

0.486

Gnomad4 NFE

AF:

0.538

Gnomad4 OTH

AF:

0.592

Alfa

AF:

0.558

Hom.:

7222

Bravo

AF:

0.602

Asia WGS

AF:

0.622

AC:

2162

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

1.1

DANN

Benign

0.37

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

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