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. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLK3	NM_001648.2	c.*886A>G		downstream_gene_variant		ENST00000326003.7	NP_001639.1
KLK3	NM_001030047.1	c.*1397A>G		downstream_gene_variant			NP_001025218.1
KLK3	NM_001030048.1	c.*886A>G		downstream_gene_variant			NP_001025219.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLK3	ENST00000326003.7	c.*886A>G		downstream_gene_variant		1	NM_001648.2	ENSP00000314151.1
KLK3	ENST00000422986.6	n.*1328A>G		downstream_gene_variant		1		ENSP00000393628.2
KLK3	ENST00000601349.5	n.*249A>G		downstream_gene_variant		1

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

Gnomad4 AFR AF: 0.657

Gnomad4 AMR AF: 0.766

Gnomad4 ASJ AF: 0.812

Gnomad4 EAS AF: 0.584

Gnomad4 SAS AF: 0.670

Gnomad4 FIN AF: 0.876

Gnomad4 NFE AF: 0.857

Gnomad4 OTH AF: 0.771

Alfa AF: 0.819 Hom.: 22516

Bravo AF: 0.761

Asia WGS AF: 0.618 AC: 2152 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2569735; hg19: chr19-51364269;