19-50857512-A-G

Variant names:

• chr19-50857512-A-G
• rs266877
• NM_001648.2:c.207-517A>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.207-517A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.943 in 155,320 control chromosomes in the GnomAD database, including 69,217 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 0.94 (67857 hom., cov: 31)
  • Exomes 𝑓: 0.93 (1360 hom.)
• Consequence: KLK3 NM_001648.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.78
• Publications: 5 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.973 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.207-517A>G		intron	N/A	NP_001639.1
	KLK3	NM_001030047.1		c.207-517A>G		intron	N/A	NP_001025218.1
	KLK3	NM_001030048.1		c.207-646A>G		intron	N/A	NP_001025219.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLK3	ENST00000326003.7	TSL:1 MANE Select	c.207-517A>G		intron	N/A	ENSP00000314151.1
	KLK3	ENST00000360617.7	TSL:1	c.207-517A>G		intron	N/A	ENSP00000353829.2
	KLK3	ENST00000593997.5	TSL:1	c.207-517A>G		intron	N/A	ENSP00000472907.1

Frequencies

GnomAD3 genomes AF: 0.943 AC: 143415 AN: 152072 Hom.: 67802 Cov.: 31

Gnomad AFR AF: 0.981

Gnomad AMI AF: 0.979

Gnomad AMR AF: 0.858

Gnomad ASJ AF: 0.908

Gnomad EAS AF: 0.848

Gnomad SAS AF: 0.858

Gnomad FIN AF: 0.973

Gnomad MID AF: 0.851

Gnomad NFE AF: 0.950

Gnomad OTH AF: 0.922

GnomAD4 exome AF: 0.930 AC: 2911 AN: 3130 Hom.: 1360 Cov.: 0 AF XY: 0.928 AC XY: 1634 AN XY: 1760

African (AFR) AF: 1.00 AC: 18 AN: 18

American (AMR) AF: 0.800 AC: 256 AN: 320

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 14 AN: 14

East Asian (EAS) AF: 0.925 AC: 37 AN: 40

South Asian (SAS) AF: 0.839 AC: 146 AN: 174

European-Finnish (FIN) AF: 0.992 AC: 125 AN: 126

Middle Eastern (MID) AF: 0.833 AC: 5 AN: 6

European-Non Finnish (NFE) AF: 0.950 AC: 2177 AN: 2292

Other (OTH) AF: 0.950 AC: 133 AN: 140

GnomAD4 genome AF: 0.943 AC: 143523 AN: 152190 Hom.: 67857 Cov.: 31 AF XY: 0.940 AC XY: 69907 AN XY: 74390

African (AFR) AF: 0.981 AC: 40761 AN: 41548

American (AMR) AF: 0.857 AC: 13091 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.908 AC: 3154 AN: 3472

East Asian (EAS) AF: 0.848 AC: 4350 AN: 5128

South Asian (SAS) AF: 0.859 AC: 4127 AN: 4806

European-Finnish (FIN) AF: 0.973 AC: 10335 AN: 10620

Middle Eastern (MID) AF: 0.837 AC: 246 AN: 294

European-Non Finnish (NFE) AF: 0.950 AC: 64613 AN: 68018

Other (OTH) AF: 0.925 AC: 1953 AN: 2112

Alfa AF: 0.946 Hom.: 94009

Bravo AF: 0.935

Asia WGS AF: 0.867 AC: 3017 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.081
DANN	Benign	0.19
PhyloP100		-4.8
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs266877; hg19: chr19-51360768;