rs1058274

Positions:

• chr19-50860192-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001648.2(KLK3):​c.*65A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 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 NM_001648.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.59

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KLK3	NM_001648.2	c.*65A>G		3_prime_UTR_variant	5/5	ENST00000326003.7
KLK3	NM_001030047.1	c.*576A>G		3_prime_UTR_variant	5/5
KLK3	NM_001030048.1	c.*65A>G		3_prime_UTR_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KLK3	ENST00000326003.7	c.*65A>G		3_prime_UTR_variant	5/5	1	NM_001648.2	P1

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

Gnomad4 AFR exome AF: 0.265

Gnomad4 AMR exome AF: 0.160

Gnomad4 ASJ exome AF: 0.284

Gnomad4 EAS exome AF: 0.0725

Gnomad4 SAS exome AF: 0.274

Gnomad4 FIN exome AF: 0.318

Gnomad4 NFE exome AF: 0.340

Gnomad4 OTH exome AF: 0.300

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

Gnomad4 AFR AF: 0.259

Gnomad4 AMR AF: 0.213

Gnomad4 ASJ AF: 0.285

Gnomad4 EAS AF: 0.0702

Gnomad4 SAS AF: 0.266

Gnomad4 FIN AF: 0.320

Gnomad4 NFE AF: 0.330

Gnomad4 OTH AF: 0.274

Alfa AF: 0.302 Hom.: 2864

Bravo AF: 0.274

Asia WGS AF: 0.148 AC: 515 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.96
DANN	Benign	0.68

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

Other links and lift over

dbSNP: rs1058274; hg19: chr19-51363448; COSMIC: COSV58100606; COSMIC: COSV58100606;