19-50858216-CTC-ATT

Variant names:

• chr19-50858216-CTC-ATT
• NM_001648.2:c.394_396delCTCinsATT
• KLK3 p.Leu132Ile

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001648.2(KLK3):​c.394_396delCTCinsATT​(p.Leu132Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Benign in ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: KLK3 NM_001648.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.376
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001648.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLK3	NM_001648.2	MANE Select	c.394_396delCTCinsATT	p.Leu132Ile	missense	N/A	NP_001639.1	Q546G3
	KLK3	NM_001030047.1		c.394_396delCTCinsATT	p.Leu132Ile	missense	N/A	NP_001025218.1	P07288-2
	KLK3	NM_001030048.1		c.265_267delCTCinsATT	p.Leu89Ile	missense	N/A	NP_001025219.1	P07288-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLK3	ENST00000326003.7	TSL:1 MANE Select	c.394_396delCTCinsATT	p.Leu132Ile	missense	N/A	ENSP00000314151.1	P07288-1
	KLK3	ENST00000360617.7	TSL:1	c.394_396delCTCinsATT	p.Leu132Ile	missense	N/A	ENSP00000353829.2	P07288-2
	KLK3	ENST00000593997.5	TSL:1	c.394_396delCTCinsATT	p.Leu132Ile	missense	N/A	ENSP00000472907.1	P07288-5

Frequencies

GnomAD3 genomes Cov.: 31

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.38

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr19-51361472;