19-50860967-C-G

Variant names:

• chr19-50860967-C-G
• rs55799315
• NM_001648.2:c.*840C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001648.2(KLK3):​c.*840C>G variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 152,078 control chromosomes in the GnomAD database, including 1,328 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 0.12 (1328 hom., cov: 32)
• Consequence: KLK3 NM_001648.2 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00400
• Publications: 4 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.153 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLK3	NM_001648.2	c.*840C>G		downstream_gene_variant		ENST00000326003.7	NP_001639.1
KLK3	NM_001030047.1	c.*1351C>G		downstream_gene_variant			NP_001025218.1
KLK3	NM_001030048.1	c.*840C>G		downstream_gene_variant			NP_001025219.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLK3	ENST00000326003.7	c.*840C>G		downstream_gene_variant		1	NM_001648.2	ENSP00000314151.1
KLK3	ENST00000422986.6	n.*1282C>G		downstream_gene_variant		1		ENSP00000393628.2
KLK3	ENST00000596333.1	n.*205C>G		downstream_gene_variant		1
KLK3	ENST00000601349.5	n.*203C>G		downstream_gene_variant		1

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18139 AN: 151960 Hom.: 1329 Cov.: 32

Gnomad AFR AF: 0.0479

Gnomad AMI AF: 0.183

Gnomad AMR AF: 0.0958

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.0411

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.230

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.118

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

GnomAD4 genome AF: 0.119 AC: 18149 AN: 152078 Hom.: 1328 Cov.: 32 AF XY: 0.122 AC XY: 9076 AN XY: 74322

African (AFR) AF: 0.0480 AC: 1992 AN: 41470

American (AMR) AF: 0.0957 AC: 1462 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.125 AC: 432 AN: 3466

East Asian (EAS) AF: 0.0414 AC: 214 AN: 5174

South Asian (SAS) AF: 0.127 AC: 610 AN: 4816

European-Finnish (FIN) AF: 0.230 AC: 2428 AN: 10570

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.155 AC: 10548 AN: 67990

Other (OTH) AF: 0.117 AC: 247 AN: 2108

Alfa AF: 0.135 Hom.: 202

Bravo AF: 0.105

Asia WGS AF: 0.0730 AC: 254 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	12
DANN	Benign	0.89
PhyloP100		-0.0040

Splicing

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

Other links and lift over

dbSNP: rs55799315; hg19: chr19-51364223;