chr19-50859281-T-G

Variant names:

• chr19-50859281-T-G
• rs62113214
• NM_001648.2:c.630+686T>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.630+686T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0489 in 151,462 control chromosomes in the GnomAD database, including 239 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 0.049 (239 hom., cov: 31)
• Consequence: KLK3 NM_001648.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17
• Publications: 8 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 = 0.0719 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLK3	NM_001648.2	MANE Select	c.630+686T>G		intron	N/A	NP_001639.1
	KLK3	NM_001030047.1		c.631-249T>G		intron	N/A	NP_001025218.1
	KLK3	NM_001030048.1		c.501+686T>G		intron	N/A	NP_001025219.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLK3	ENST00000326003.7	TSL:1 MANE Select	c.630+686T>G		intron	N/A	ENSP00000314151.1
	KLK3	ENST00000360617.7	TSL:1	c.631-249T>G		intron	N/A	ENSP00000353829.2
	KLK3	ENST00000422986.6	TSL:1	n.*286+686T>G		intron	N/A	ENSP00000393628.2

Frequencies

GnomAD3 genomes AF: 0.0490 AC: 7410 AN: 151344 Hom.: 240 Cov.: 31

Gnomad AFR AF: 0.0124

Gnomad AMI AF: 0.187

Gnomad AMR AF: 0.0333

Gnomad ASJ AF: 0.0780

Gnomad EAS AF: 0.000973

Gnomad SAS AF: 0.0543

Gnomad FIN AF: 0.0552

Gnomad MID AF: 0.0605

Gnomad NFE AF: 0.0736

Gnomad OTH AF: 0.0489

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

GnomAD4 genome AF: 0.0489 AC: 7412 AN: 151462 Hom.: 239 Cov.: 31 AF XY: 0.0475 AC XY: 3517 AN XY: 73992

African (AFR) AF: 0.0124 AC: 512 AN: 41280

American (AMR) AF: 0.0332 AC: 507 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.0780 AC: 270 AN: 3462

East Asian (EAS) AF: 0.000975 AC: 5 AN: 5126

South Asian (SAS) AF: 0.0543 AC: 260 AN: 4786

European-Finnish (FIN) AF: 0.0552 AC: 579 AN: 10496

Middle Eastern (MID) AF: 0.0651 AC: 19 AN: 292

European-Non Finnish (NFE) AF: 0.0736 AC: 4988 AN: 67752

Other (OTH) AF: 0.0484 AC: 102 AN: 2106

Alfa AF: 0.0570 Hom.: 39

Bravo AF: 0.0469

Asia WGS AF: 0.0150 AC: 52 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	1.1
DANN	Benign	0.63
PhyloP100		-1.2
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: rs62113214; hg19: chr19-51362537;