19-50859048-C-T

Variant names:

• chr19-50859048-C-T
• rs11084034
• NM_001648.2:c.630+453C>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.630+453C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 227,216 control chromosomes in the GnomAD database, including 11,669 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 0.28 (7218 hom., cov: 29)
  • Exomes 𝑓: 0.32 (4451 hom.)
• Consequence: KLK3 NM_001648.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.89
• Publications: 3 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 (EAS) allele frequency at 95% confidence interval = 0.414 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.630+453C>T		intron	N/A	NP_001639.1	Q546G3
	KLK3	NM_001030047.1		c.630+453C>T		intron	N/A	NP_001025218.1	P07288-2
	KLK3	NM_001030048.1		c.501+453C>T		intron	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.630+453C>T		intron	N/A	ENSP00000314151.1	P07288-1
	KLK3	ENST00000360617.7	TSL:1	c.630+453C>T		intron	N/A	ENSP00000353829.2	P07288-2
	KLK3	ENST00000422986.6	TSL:1	n.*286+453C>T		intron	N/A	ENSP00000393628.2	A0A0B4J1X3

Frequencies

GnomAD3 genomes AF: 0.281 AC: 42536 AN: 151372 Hom.: 7214 Cov.: 29

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.249

Gnomad AMR AF: 0.371

Gnomad ASJ AF: 0.251

Gnomad EAS AF: 0.429

Gnomad SAS AF: 0.182

Gnomad FIN AF: 0.460

Gnomad MID AF: 0.220

Gnomad NFE AF: 0.335

Gnomad OTH AF: 0.267

GnomAD4 exome AF: 0.325 AC: 24599 AN: 75726 Hom.: 4451 AF XY: 0.322 AC XY: 12381 AN XY: 38498

African (AFR) AF: 0.103 AC: 309 AN: 2998

American (AMR) AF: 0.387 AC: 1569 AN: 4058

Ashkenazi Jewish (ASJ) AF: 0.234 AC: 627 AN: 2680

East Asian (EAS) AF: 0.432 AC: 2436 AN: 5642

South Asian (SAS) AF: 0.173 AC: 512 AN: 2960

European-Finnish (FIN) AF: 0.478 AC: 1811 AN: 3786

Middle Eastern (MID) AF: 0.192 AC: 64 AN: 334

European-Non Finnish (NFE) AF: 0.326 AC: 15812 AN: 48450

Other (OTH) AF: 0.303 AC: 1459 AN: 4818

GnomAD4 genome AF: 0.281 AC: 42555 AN: 151490 Hom.: 7218 Cov.: 29 AF XY: 0.285 AC XY: 21072 AN XY: 73994

African (AFR) AF: 0.112 AC: 4610 AN: 41324

American (AMR) AF: 0.371 AC: 5661 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.251 AC: 869 AN: 3464

East Asian (EAS) AF: 0.429 AC: 2175 AN: 5074

South Asian (SAS) AF: 0.181 AC: 867 AN: 4778

European-Finnish (FIN) AF: 0.460 AC: 4837 AN: 10518

Middle Eastern (MID) AF: 0.209 AC: 61 AN: 292

European-Non Finnish (NFE) AF: 0.335 AC: 22675 AN: 67778

Other (OTH) AF: 0.273 AC: 574 AN: 2100

Alfa AF: 0.273 Hom.: 1254

Bravo AF: 0.267

Asia WGS AF: 0.302 AC: 1048 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.19
DANN	Benign	0.56
PhyloP100		-2.9
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: rs11084034; hg19: chr19-51362304;