ENST00000596185.5:n.*112C>G

Variant names:

• chr19-50855382-C-G
• rs266879
• ENST00000596185.5:n.*112C>G

Variant summary

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

The ENST00000596185.5(KLK3):​n.*112C>G 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 0.331 in 232,162 control chromosomes in the GnomAD database, including 13,287 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 0.33 (8560 hom., cov: 31)
  • Exomes 𝑓: 0.34 (4727 hom.)
• Consequence: KLK3 ENST00000596185.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.29
• Publications: 4 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.374 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000596185.5. 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.46+381C>G		intron	N/A	NP_001639.1
	KLK3	NM_001030047.1		c.46+381C>G		intron	N/A	NP_001025218.1
	KLK3	NM_001030048.1		c.46+381C>G		intron	N/A	NP_001025219.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLK3	ENST00000596185.5	TSL:1	n.*112C>G		non_coding_transcript_exon	Exon 1 of 5	ENSP00000471648.1
	KLK3	ENST00000601349.5	TSL:1	n.468C>G		non_coding_transcript_exon	Exon 1 of 4
	KLK3	ENST00000596185.5	TSL:1	n.*112C>G		3_prime_UTR	Exon 1 of 5	ENSP00000471648.1

Frequencies

GnomAD3 genomes AF: 0.327 AC: 49713 AN: 151908 Hom.: 8557 Cov.: 31

Gnomad AFR AF: 0.293

Gnomad AMI AF: 0.302

Gnomad AMR AF: 0.260

Gnomad ASJ AF: 0.340

Gnomad EAS AF: 0.0685

Gnomad SAS AF: 0.260

Gnomad FIN AF: 0.386

Gnomad MID AF: 0.362

Gnomad NFE AF: 0.378

Gnomad OTH AF: 0.327

GnomAD4 exome AF: 0.338 AC: 27123 AN: 80132 Hom.: 4727 Cov.: 0 AF XY: 0.334 AC XY: 13965 AN XY: 41768

African (AFR) AF: 0.293 AC: 768 AN: 2620

American (AMR) AF: 0.224 AC: 990 AN: 4422

Ashkenazi Jewish (ASJ) AF: 0.324 AC: 813 AN: 2510

East Asian (EAS) AF: 0.0734 AC: 325 AN: 4428

South Asian (SAS) AF: 0.278 AC: 2260 AN: 8136

European-Finnish (FIN) AF: 0.385 AC: 1411 AN: 3668

Middle Eastern (MID) AF: 0.355 AC: 130 AN: 366

European-Non Finnish (NFE) AF: 0.381 AC: 18791 AN: 49296

Other (OTH) AF: 0.349 AC: 1635 AN: 4686

GnomAD4 genome AF: 0.327 AC: 49740 AN: 152030 Hom.: 8560 Cov.: 31 AF XY: 0.324 AC XY: 24091 AN XY: 74316

African (AFR) AF: 0.294 AC: 12167 AN: 41444

American (AMR) AF: 0.260 AC: 3971 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.340 AC: 1179 AN: 3472

East Asian (EAS) AF: 0.0690 AC: 357 AN: 5174

South Asian (SAS) AF: 0.261 AC: 1259 AN: 4824

European-Finnish (FIN) AF: 0.386 AC: 4078 AN: 10566

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.378 AC: 25672 AN: 67962

Other (OTH) AF: 0.323 AC: 678 AN: 2102

Alfa AF: 0.238 Hom.: 573

Bravo AF: 0.316

Asia WGS AF: 0.151 AC: 525 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.034
DANN	Benign	0.55
PhyloP100		-3.3
PromoterAI		-0.0032	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs266879; hg19: chr19-51358638;