19-50857562-C-T

Variant names:

• chr19-50857562-C-T
• rs266876
• ENST00000601812.1:n.172C>T

Variant summary

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

The ENST00000601812.1(KLK3):​n.172C>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 0.678 in 158,184 control chromosomes in the GnomAD database, including 36,728 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 0.68 (35289 hom., cov: 30)
  • Exomes 𝑓: 0.67 (1439 hom.)
• Consequence: KLK3 ENST00000601812.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.486
• Publications: 5 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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.719 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000601812.1. 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.207-467C>T		intron	N/A	NP_001639.1
	KLK3	NM_001030047.1		c.207-467C>T		intron	N/A	NP_001025218.1
	KLK3	NM_001030048.1		c.207-596C>T		intron	N/A	NP_001025219.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLK3	ENST00000601812.1	TSL:1	n.172C>T		non_coding_transcript_exon	Exon 1 of 3
	KLK3	ENST00000326003.7	TSL:1 MANE Select	c.207-467C>T		intron	N/A	ENSP00000314151.1
	KLK3	ENST00000360617.7	TSL:1	c.207-467C>T		intron	N/A	ENSP00000353829.2

Frequencies

GnomAD3 genomes AF: 0.678 AC: 102941 AN: 151794 Hom.: 35276 Cov.: 30

Gnomad AFR AF: 0.619

Gnomad AMI AF: 0.593

Gnomad AMR AF: 0.661

Gnomad ASJ AF: 0.612

Gnomad EAS AF: 0.514

Gnomad SAS AF: 0.559

Gnomad FIN AF: 0.806

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.725

Gnomad OTH AF: 0.646

GnomAD4 exome AF: 0.669 AC: 4194 AN: 6272 Hom.: 1439 Cov.: 0 AF XY: 0.656 AC XY: 2221 AN XY: 3384

African (AFR) AF: 0.575 AC: 23 AN: 40

American (AMR) AF: 0.632 AC: 485 AN: 768

Ashkenazi Jewish (ASJ) AF: 0.688 AC: 44 AN: 64

East Asian (EAS) AF: 0.431 AC: 56 AN: 130

South Asian (SAS) AF: 0.480 AC: 234 AN: 488

European-Finnish (FIN) AF: 0.829 AC: 204 AN: 246

Middle Eastern (MID) AF: 0.625 AC: 15 AN: 24

European-Non Finnish (NFE) AF: 0.694 AC: 2928 AN: 4222

Other (OTH) AF: 0.707 AC: 205 AN: 290

GnomAD4 genome AF: 0.678 AC: 103005 AN: 151912 Hom.: 35289 Cov.: 30 AF XY: 0.677 AC XY: 50257 AN XY: 74256

African (AFR) AF: 0.619 AC: 25622 AN: 41382

American (AMR) AF: 0.661 AC: 10089 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.612 AC: 2120 AN: 3466

East Asian (EAS) AF: 0.514 AC: 2642 AN: 5142

South Asian (SAS) AF: 0.559 AC: 2683 AN: 4798

European-Finnish (FIN) AF: 0.806 AC: 8533 AN: 10586

Middle Eastern (MID) AF: 0.599 AC: 176 AN: 294

European-Non Finnish (NFE) AF: 0.724 AC: 49234 AN: 67956

Other (OTH) AF: 0.648 AC: 1368 AN: 2110

Alfa AF: 0.707 Hom.: 20616

Bravo AF: 0.662

Asia WGS AF: 0.543 AC: 1888 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.28
DANN	Benign	0.62
PhyloP100		-0.49
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: rs266876; hg19: chr19-51360818;