19-50859048-C-T

Position:

• chr19-50859048-C-T

Variant summary

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

The NM_001648.2(KLK3):​c.630+453C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 227,216 control chromosomes in the GnomAD database, including 11,669 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 0.28 (7218 hom., cov: 29)
  • Exomes 𝑓: 0.32 (4451 hom.)
• Consequence: KLK3 NM_001648.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.89

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 (EAS) allele frequency at 95% confidence interval = 0.414 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLK3	NM_001648.2	c.630+453C>T		intron_variant		ENST00000326003.7	NP_001639.1
KLK3	NM_001030047.1	c.630+453C>T		intron_variant			NP_001025218.1
KLK3	NM_001030048.1	c.501+453C>T		intron_variant			NP_001025219.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLK3	ENST00000326003.7	c.630+453C>T		intron_variant		1	NM_001648.2	ENSP00000314151	P1

Frequencies

GnomAD3 genomes AF: 0.281 AC: 42536 AN: 151372 Hom.: 7214 Cov.: 29

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.249

Gnomad AMR AF: 0.371

Gnomad ASJ AF: 0.251

Gnomad EAS AF: 0.429

Gnomad SAS AF: 0.182

Gnomad FIN AF: 0.460

Gnomad MID AF: 0.220

Gnomad NFE AF: 0.335

Gnomad OTH AF: 0.267

GnomAD4 exome AF: 0.325 AC: 24599 AN: 75726 Hom.: 4451 AF XY: 0.322 AC XY: 12381 AN XY: 38498

Gnomad4 AFR exome AF: 0.103

Gnomad4 AMR exome AF: 0.387

Gnomad4 ASJ exome AF: 0.234

Gnomad4 EAS exome AF: 0.432

Gnomad4 SAS exome AF: 0.173

Gnomad4 FIN exome AF: 0.478

Gnomad4 NFE exome AF: 0.326

Gnomad4 OTH exome AF: 0.303

GnomAD4 genome AF: 0.281 AC: 42555 AN: 151490 Hom.: 7218 Cov.: 29 AF XY: 0.285 AC XY: 21072 AN XY: 73994

Gnomad4 AFR AF: 0.112

Gnomad4 AMR AF: 0.371

Gnomad4 ASJ AF: 0.251

Gnomad4 EAS AF: 0.429

Gnomad4 SAS AF: 0.181

Gnomad4 FIN AF: 0.460

Gnomad4 NFE AF: 0.335

Gnomad4 OTH AF: 0.273

Alfa AF: 0.277 Hom.: 1249

Bravo AF: 0.267

Asia WGS AF: 0.302 AC: 1048 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.19
DANN	Benign	0.56

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: rs11084034; hg19: chr19-51362304;