chr19-50860984-T-C

Variant names:

• chr19-50860984-T-C
• rs4802755
• NM_001648.2:c.*857T>C

Variant summary

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

The NM_001648.2(KLK3):​c.*857T>C variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 152,016 control chromosomes in the GnomAD database, including 14,423 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 0.40 (14423 hom., cov: 31)
• Consequence: KLK3 NM_001648.2 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.537
• 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=-0.75).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.487 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLK3	NM_001648.2	c.*857T>C		downstream_gene_variant		ENST00000326003.7	NP_001639.1
KLK3	NM_001030047.1	c.*1368T>C		downstream_gene_variant			NP_001025218.1
KLK3	NM_001030048.1	c.*857T>C		downstream_gene_variant			NP_001025219.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLK3	ENST00000326003.7	c.*857T>C		downstream_gene_variant		1	NM_001648.2	ENSP00000314151.1
KLK3	ENST00000422986.6	n.*1299T>C		downstream_gene_variant		1		ENSP00000393628.2
KLK3	ENST00000596333.1	n.*222T>C		downstream_gene_variant		1
KLK3	ENST00000601349.5	n.*220T>C		downstream_gene_variant		1

Frequencies

GnomAD3 genomes AF: 0.404 AC: 61390 AN: 151898 Hom.: 14419 Cov.: 31

Gnomad AFR AF: 0.168

Gnomad AMI AF: 0.435

Gnomad AMR AF: 0.473

Gnomad ASJ AF: 0.375

Gnomad EAS AF: 0.471

Gnomad SAS AF: 0.312

Gnomad FIN AF: 0.690

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.491

Gnomad OTH AF: 0.387

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

GnomAD4 genome AF: 0.404 AC: 61414 AN: 152016 Hom.: 14423 Cov.: 31 AF XY: 0.410 AC XY: 30474 AN XY: 74276

African (AFR) AF: 0.168 AC: 6952 AN: 41460

American (AMR) AF: 0.473 AC: 7230 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.375 AC: 1301 AN: 3472

East Asian (EAS) AF: 0.470 AC: 2424 AN: 5156

South Asian (SAS) AF: 0.312 AC: 1501 AN: 4810

European-Finnish (FIN) AF: 0.690 AC: 7286 AN: 10562

Middle Eastern (MID) AF: 0.373 AC: 109 AN: 292

European-Non Finnish (NFE) AF: 0.491 AC: 33386 AN: 67958

Other (OTH) AF: 0.392 AC: 828 AN: 2110

Alfa AF: 0.457 Hom.: 10186

Bravo AF: 0.377

Asia WGS AF: 0.382 AC: 1327 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	8.7
DANN	Benign	0.93
PhyloP100		-0.54

Splicing

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

Other links and lift over

dbSNP: rs4802755; hg19: chr19-51364240;