19-50860192-A-G

Variant names:

• chr19-50860192-A-G
• rs1058274
• ENST00000422986.6:n.*507A>G

Variant summary

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

The ENST00000422986.6(KLK3):​n.*507A>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 0.312 in 1,295,496 control chromosomes in the GnomAD database, including 65,254 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 (6490 hom., cov: 33)
  • Exomes 𝑓: 0.32 (58764 hom.)
• Consequence: KLK3 ENST00000422986.6 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.59
• Publications: 13 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.327 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000422986.6. 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.*65A>G		3_prime_UTR	Exon 5 of 5	NP_001639.1
	KLK3	NM_001030047.1		c.*576A>G		3_prime_UTR	Exon 5 of 5	NP_001025218.1
	KLK3	NM_001030048.1		c.*65A>G		3_prime_UTR	Exon 5 of 5	NP_001025219.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLK3	ENST00000422986.6	TSL:1	n.*507A>G		non_coding_transcript_exon	Exon 6 of 6	ENSP00000393628.2
	KLK3	ENST00000596333.1	TSL:1	n.1029A>G		non_coding_transcript_exon	Exon 4 of 4
	KLK3	ENST00000601349.5	TSL:1	n.2130A>G		non_coding_transcript_exon	Exon 4 of 4

Frequencies

GnomAD3 genomes AF: 0.286 AC: 43434 AN: 152062 Hom.: 6486 Cov.: 33

Gnomad AFR AF: 0.259

Gnomad AMI AF: 0.323

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.285

Gnomad EAS AF: 0.0696

Gnomad SAS AF: 0.266

Gnomad FIN AF: 0.320

Gnomad MID AF: 0.322

Gnomad NFE AF: 0.330

Gnomad OTH AF: 0.278

GnomAD4 exome AF: 0.315 AC: 360246 AN: 1143316 Hom.: 58764 Cov.: 15 AF XY: 0.315 AC XY: 180090 AN XY: 572600

African (AFR) AF: 0.265 AC: 7150 AN: 26986

American (AMR) AF: 0.160 AC: 6185 AN: 38596

Ashkenazi Jewish (ASJ) AF: 0.284 AC: 5845 AN: 20610

East Asian (EAS) AF: 0.0725 AC: 2734 AN: 37732

South Asian (SAS) AF: 0.274 AC: 19451 AN: 70956

European-Finnish (FIN) AF: 0.318 AC: 16219 AN: 51064

Middle Eastern (MID) AF: 0.295 AC: 1470 AN: 4988

European-Non Finnish (NFE) AF: 0.340 AC: 286466 AN: 843276

Other (OTH) AF: 0.300 AC: 14726 AN: 49108

GnomAD4 genome AF: 0.286 AC: 43457 AN: 152180 Hom.: 6490 Cov.: 33 AF XY: 0.283 AC XY: 21024 AN XY: 74420

African (AFR) AF: 0.259 AC: 10754 AN: 41508

American (AMR) AF: 0.213 AC: 3255 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.285 AC: 991 AN: 3472

East Asian (EAS) AF: 0.0702 AC: 364 AN: 5186

South Asian (SAS) AF: 0.266 AC: 1283 AN: 4818

European-Finnish (FIN) AF: 0.320 AC: 3388 AN: 10596

Middle Eastern (MID) AF: 0.322 AC: 94 AN: 292

European-Non Finnish (NFE) AF: 0.330 AC: 22456 AN: 67998

Other (OTH) AF: 0.274 AC: 578 AN: 2108

Alfa AF: 0.303 Hom.: 3436

Bravo AF: 0.274

Asia WGS AF: 0.148 AC: 515 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.96
DANN	Benign	0.68
PhyloP100		-1.6
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: rs1058274; hg19: chr19-51363448; COSMIC: COSV58100606; COSMIC: COSV58100606;