19-50858681-G-A

Variant names:

• chr19-50858681-G-A
• rs266875
• ENST00000593997.5:c.*32G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.561
• Publications: 9 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000593997.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLK3	NM_001648.2	MANE Select	c.630+86G>A		intron	N/A	NP_001639.1
	KLK3	NM_001030047.1		c.630+86G>A		intron	N/A	NP_001025218.1
	KLK3	NM_001030048.1		c.501+86G>A		intron	N/A	NP_001025219.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLK3	ENST00000593997.5	TSL:1	c.*32G>A		3_prime_UTR	Exon 4 of 4	ENSP00000472907.1
	KLK3	ENST00000326003.7	TSL:1 MANE Select	c.630+86G>A		intron	N/A	ENSP00000314151.1
	KLK3	ENST00000360617.7	TSL:1	c.630+86G>A		intron	N/A	ENSP00000353829.2

Frequencies

GnomAD3 genomes AF: 0.596 AC: 90478 AN: 151892 Hom.: 27895 Cov.: 31

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

GnomAD2 exomes AF: 0.565 AC: 120919 AN: 214090 AF XY: 0.574

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 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.: 19 AF XY: 0.558 AC XY: 372585 AN XY: 667972

African (AFR) AF: 0.762 AC: 23741 AN: 31140

American (AMR) AF: 0.472 AC: 19302 AN: 40886

Ashkenazi Jewish (ASJ) AF: 0.534 AC: 12360 AN: 23160

East Asian (EAS) AF: 0.492 AC: 19079 AN: 38792

South Asian (SAS) AF: 0.718 AC: 56672 AN: 78974

European-Finnish (FIN) AF: 0.492 AC: 24463 AN: 49772

Middle Eastern (MID) AF: 0.611 AC: 3315 AN: 5422

European-Non Finnish (NFE) AF: 0.542 AC: 553373 AN: 1020282

Other (OTH) AF: 0.563 AC: 31548 AN: 56000

GnomAD4 genome AF: 0.596 AC: 90563 AN: 152010 Hom.: 27928 Cov.: 31 AF XY: 0.596 AC XY: 44281 AN XY: 74286

African (AFR) AF: 0.750 AC: 31124 AN: 41480

American (AMR) AF: 0.513 AC: 7836 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.531 AC: 1844 AN: 3470

East Asian (EAS) AF: 0.500 AC: 2569 AN: 5140

South Asian (SAS) AF: 0.730 AC: 3521 AN: 4826

European-Finnish (FIN) AF: 0.486 AC: 5126 AN: 10548

Middle Eastern (MID) AF: 0.636 AC: 187 AN: 294

European-Non Finnish (NFE) AF: 0.538 AC: 36585 AN: 67946

Other (OTH) AF: 0.592 AC: 1252 AN: 2114

Alfa AF: 0.570 Hom.: 8461

Bravo AF: 0.602

Asia WGS AF: 0.622 AC: 2162 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.1
DANN	Benign	0.37
PhyloP100		-0.56
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs266875; hg19: chr19-51361937; COSMIC: COSV58100792; COSMIC: COSV58100792;