rs2569735

Variant names:

• chr19-50861013-A-G
• rs2569735
• NM_001648.2:c.*886A>G

Your query was ambiguous. Multiple possible variants found:

• chr19-50861013-A-G
• chr19-50861013-A-T

Variant summary

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

The NM_001648.2(KLK3):​c.*886A>G variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.777 in 151,932 control chromosomes in the GnomAD database, including 46,634 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 0.78 (46634 hom., cov: 30)
• Consequence: KLK3 NM_001648.2 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.649
• Publications: 12 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.852 is higher than 0.05.

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.*886A>G		downstream_gene	N/A	NP_001639.1	Q546G3
	KLK3	NM_001030047.1		c.*1397A>G		downstream_gene	N/A	NP_001025218.1	P07288-2
	KLK3	NM_001030048.1		c.*886A>G		downstream_gene	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.*886A>G		downstream_gene	N/A	ENSP00000314151.1	P07288-1
	KLK3	ENST00000422986.6	TSL:1	n.*1328A>G		downstream_gene	N/A	ENSP00000393628.2	A0A0B4J1X3
	KLK3	ENST00000601349.5	TSL:1	n.*249A>G		downstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.777 AC: 117955 AN: 151814 Hom.: 46612 Cov.: 30

Gnomad AFR AF: 0.657

Gnomad AMI AF: 0.776

Gnomad AMR AF: 0.767

Gnomad ASJ AF: 0.812

Gnomad EAS AF: 0.584

Gnomad SAS AF: 0.669

Gnomad FIN AF: 0.876

Gnomad MID AF: 0.758

Gnomad NFE AF: 0.857

Gnomad OTH AF: 0.770

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

GnomAD4 genome AF: 0.777 AC: 118026 AN: 151932 Hom.: 46634 Cov.: 30 AF XY: 0.774 AC XY: 57441 AN XY: 74260

African (AFR) AF: 0.657 AC: 27193 AN: 41388

American (AMR) AF: 0.766 AC: 11702 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.812 AC: 2816 AN: 3466

East Asian (EAS) AF: 0.584 AC: 3010 AN: 5152

South Asian (SAS) AF: 0.670 AC: 3227 AN: 4814

European-Finnish (FIN) AF: 0.876 AC: 9272 AN: 10582

Middle Eastern (MID) AF: 0.740 AC: 216 AN: 292

European-Non Finnish (NFE) AF: 0.857 AC: 58263 AN: 67950

Other (OTH) AF: 0.771 AC: 1621 AN: 2102

Alfa AF: 0.823 Hom.: 37161

Bravo AF: 0.761

Asia WGS AF: 0.618 AC: 2152 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.6
DANN	Benign	0.83
PhyloP100		-0.65

Splicing

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

Other links and lift over

dbSNP: rs2569735; hg19: chr19-51364269;