chr19-50857562-C-T

Position:

• chr19-50857562-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.207-467C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.678 in 158,184 control chromosomes in the GnomAD database, including 36,728 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 0.68 (35289 hom., cov: 30)
  • Exomes 𝑓: 0.67 (1439 hom.)
• Consequence: KLK3 NM_001648.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.486

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]

KLK3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.719 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLK3	NM_001648.2	c.207-467C>T		intron_variant		ENST00000326003.7	NP_001639.1
KLK3	NM_001030047.1	c.207-467C>T		intron_variant			NP_001025218.1
KLK3	NM_001030048.1	c.207-596C>T		intron_variant			NP_001025219.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLK3	ENST00000326003.7	c.207-467C>T		intron_variant		1	NM_001648.2	ENSP00000314151.1

Frequencies

GnomAD3 genomes AF: 0.678 AC: 102941 AN: 151794 Hom.: 35276 Cov.: 30

Gnomad AFR AF: 0.619

Gnomad AMI AF: 0.593

Gnomad AMR AF: 0.661

Gnomad ASJ AF: 0.612

Gnomad EAS AF: 0.514

Gnomad SAS AF: 0.559

Gnomad FIN AF: 0.806

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.725

Gnomad OTH AF: 0.646

GnomAD4 exome AF: 0.669 AC: 4194 AN: 6272 Hom.: 1439 Cov.: 0 AF XY: 0.656 AC XY: 2221 AN XY: 3384

Gnomad4 AFR exome AF: 0.575

Gnomad4 AMR exome AF: 0.632

Gnomad4 ASJ exome AF: 0.688

Gnomad4 EAS exome AF: 0.431

Gnomad4 SAS exome AF: 0.480

Gnomad4 FIN exome AF: 0.829

Gnomad4 NFE exome AF: 0.694

Gnomad4 OTH exome AF: 0.707

GnomAD4 genome AF: 0.678 AC: 103005 AN: 151912 Hom.: 35289 Cov.: 30 AF XY: 0.677 AC XY: 50257 AN XY: 74256

Gnomad4 AFR AF: 0.619

Gnomad4 AMR AF: 0.661

Gnomad4 ASJ AF: 0.612

Gnomad4 EAS AF: 0.514

Gnomad4 SAS AF: 0.559

Gnomad4 FIN AF: 0.806

Gnomad4 NFE AF: 0.724

Gnomad4 OTH AF: 0.648

Alfa AF: 0.704 Hom.: 11874

Bravo AF: 0.662

Asia WGS AF: 0.543 AC: 1888 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.28
DANN	Benign	0.62

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: rs266876; hg19: chr19-51360818;