19-50856287-G-T

Variant names:

• chr19-50856287-G-T
• rs2271092
• NM_001648.2:c.94G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001648.2(KLK3):​c.94G>T​(p.Glu32*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: KLK3 NM_001648.2 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.38
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.94G>T	p.Glu32*	stop_gained	Exon 2 of 5	NP_001639.1	Q546G3
	KLK3	NM_001030047.1		c.94G>T	p.Glu32*	stop_gained	Exon 2 of 5	NP_001025218.1	P07288-2
	KLK3	NM_001030048.1		c.94G>T	p.Glu32*	stop_gained	Exon 2 of 5	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.94G>T	p.Glu32*	stop_gained	Exon 2 of 5	ENSP00000314151.1	P07288-1
	KLK3	ENST00000360617.7	TSL:1	c.94G>T	p.Glu32*	stop_gained	Exon 2 of 5	ENSP00000353829.2	P07288-2
	KLK3	ENST00000593997.5	TSL:1	c.94G>T	p.Glu32*	stop_gained	Exon 2 of 4	ENSP00000472907.1	P07288-5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Pathogenic	32
DANN	Benign	0.96
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.022	N
PhyloP100		-3.4
Vest4		0.72
GERP RS		-4.2
Mutation Taster		=57/143	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.22		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.22		Position offset: -47

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

Other links and lift over

dbSNP: rs2271092; hg19: chr19-51359543; COSMIC: COSV58098770; COSMIC: COSV58098770;