19-50855432-C-G

Variant names:

• chr19-50855432-C-G
• rs2292185
• ENST00000601349.5:n.518C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000601349.5(KLK3):​n.518C>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: KLK3 ENST00000601349.5 non_coding_transcript_exon
• Scores: Splicing: ADA: 0.00005103
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.599
• Publications: 8 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLK3	NM_001648.2	c.46+431C>G		intron_variant	Intron 1 of 4	ENST00000326003.7	NP_001639.1
KLK3	NM_001030047.1	c.46+431C>G		intron_variant	Intron 1 of 4		NP_001025218.1
KLK3	NM_001030048.1	c.46+431C>G		intron_variant	Intron 1 of 4		NP_001025219.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLK3	ENST00000326003.7	c.46+431C>G		intron_variant	Intron 1 of 4	1	NM_001648.2	ENSP00000314151.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 17490 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 9298

African (AFR) AF: 0.00 AC: 0 AN: 414

American (AMR) AF: 0.00 AC: 0 AN: 1936

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 468

East Asian (EAS) AF: 0.00 AC: 0 AN: 704

South Asian (SAS) AF: 0.00 AC: 0 AN: 1550

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 574

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 52

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 10854

Other (OTH) AF: 0.00 AC: 0 AN: 938

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.0
DANN	Benign	0.25
PhyloP100		-0.60
PromoterAI		-0.015	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000051
dbscSNV1_RF	Benign	0.0
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

Other links and lift over

dbSNP: rs2292185; hg19: chr19-51358688;