rs1061477

Positions:

• chr19-50856840-T-C

Variant summary

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

The ENST00000326003.7(KLK3):​c.206+441T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.418 in 159,114 control chromosomes in the GnomAD database, including 15,160 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 0.42 (14487 hom., cov: 28)
  • Exomes 𝑓: 0.37 (673 hom.)
• Consequence: KLK3 ENST00000326003.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.175

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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.494 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLK3	NM_001648.2	c.206+441T>C		intron_variant		ENST00000326003.7	NP_001639.1
KLK3	NM_001030047.1	c.206+441T>C		intron_variant			NP_001025218.1
KLK3	NM_001030048.1	c.206+441T>C		intron_variant			NP_001025219.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLK3	ENST00000326003.7	c.206+441T>C		intron_variant		1	NM_001648.2	ENSP00000314151	P1

Frequencies

GnomAD3 genomes AF: 0.421 AC: 63509 AN: 150864 Hom.: 14483 Cov.: 28

Gnomad AFR AF: 0.243

Gnomad AMI AF: 0.630

Gnomad AMR AF: 0.489

Gnomad ASJ AF: 0.476

Gnomad EAS AF: 0.503

Gnomad SAS AF: 0.280

Gnomad FIN AF: 0.513

Gnomad MID AF: 0.388

Gnomad NFE AF: 0.498

Gnomad OTH AF: 0.424

GnomAD4 exome AF: 0.368 AC: 2994 AN: 8130 Hom.: 673 AF XY: 0.366 AC XY: 1630 AN XY: 4450

Gnomad4 AFR exome AF: 0.226

Gnomad4 AMR exome AF: 0.428

Gnomad4 ASJ exome AF: 0.291

Gnomad4 EAS exome AF: 0.407

Gnomad4 SAS exome AF: 0.173

Gnomad4 FIN exome AF: 0.395

Gnomad4 NFE exome AF: 0.394

Gnomad4 OTH exome AF: 0.347

GnomAD4 genome AF: 0.421 AC: 63536 AN: 150984 Hom.: 14487 Cov.: 28 AF XY: 0.418 AC XY: 30810 AN XY: 73710

Gnomad4 AFR AF: 0.242

Gnomad4 AMR AF: 0.489

Gnomad4 ASJ AF: 0.476

Gnomad4 EAS AF: 0.503

Gnomad4 SAS AF: 0.280

Gnomad4 FIN AF: 0.513

Gnomad4 NFE AF: 0.498

Gnomad4 OTH AF: 0.428

Alfa AF: 0.479 Hom.: 9021

Bravo AF: 0.418

Asia WGS AF: 0.373 AC: 1299 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	3.4
DANN	Benign	0.28

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: rs1061477; hg19: chr19-51360096;