chr19-50856840-T-C

Variant names:

• chr19-50856840-T-C
• rs1061477
• NM_001648.2:c.206+441T>C

Variant summary

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

The NM_001648.2(KLK3):​c.206+441T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.418 in 159,114 control chromosomes in the GnomAD database, including 15,160 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 0.42 (14487 hom., cov: 28)
  • Exomes 𝑓: 0.37 (673 hom.)
• Consequence: KLK3 NM_001648.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.175
• 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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.494 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.206+441T>C		intron	N/A	NP_001639.1
	KLK3	NM_001030047.1		c.206+441T>C		intron	N/A	NP_001025218.1
	KLK3	NM_001030048.1		c.206+441T>C		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.206+441T>C		intron	N/A	ENSP00000314151.1
	KLK3	ENST00000360617.7	TSL:1	c.206+441T>C		intron	N/A	ENSP00000353829.2
	KLK3	ENST00000593997.5	TSL:1	c.206+441T>C		intron	N/A	ENSP00000472907.1

Frequencies

GnomAD3 genomes AF: 0.421 AC: 63509 AN: 150864 Hom.: 14483 Cov.: 28

Gnomad AFR AF: 0.243

Gnomad AMI AF: 0.630

Gnomad AMR AF: 0.489

Gnomad ASJ AF: 0.476

Gnomad EAS AF: 0.503

Gnomad SAS AF: 0.280

Gnomad FIN AF: 0.513

Gnomad MID AF: 0.388

Gnomad NFE AF: 0.498

Gnomad OTH AF: 0.424

GnomAD4 exome AF: 0.368 AC: 2994 AN: 8130 Hom.: 673 AF XY: 0.366 AC XY: 1630 AN XY: 4450

African (AFR) AF: 0.226 AC: 28 AN: 124

American (AMR) AF: 0.428 AC: 260 AN: 608

Ashkenazi Jewish (ASJ) AF: 0.291 AC: 53 AN: 182

East Asian (EAS) AF: 0.407 AC: 57 AN: 140

South Asian (SAS) AF: 0.173 AC: 134 AN: 774

European-Finnish (FIN) AF: 0.395 AC: 87 AN: 220

Middle Eastern (MID) AF: 0.423 AC: 11 AN: 26

European-Non Finnish (NFE) AF: 0.394 AC: 2200 AN: 5584

Other (OTH) AF: 0.347 AC: 164 AN: 472

GnomAD4 genome AF: 0.421 AC: 63536 AN: 150984 Hom.: 14487 Cov.: 28 AF XY: 0.418 AC XY: 30810 AN XY: 73710

African (AFR) AF: 0.242 AC: 9982 AN: 41198

American (AMR) AF: 0.489 AC: 7420 AN: 15178

Ashkenazi Jewish (ASJ) AF: 0.476 AC: 1649 AN: 3464

East Asian (EAS) AF: 0.503 AC: 2540 AN: 5054

South Asian (SAS) AF: 0.280 AC: 1338 AN: 4780

European-Finnish (FIN) AF: 0.513 AC: 5350 AN: 10438

Middle Eastern (MID) AF: 0.376 AC: 109 AN: 290

European-Non Finnish (NFE) AF: 0.498 AC: 33696 AN: 67608

Other (OTH) AF: 0.428 AC: 893 AN: 2086

Alfa AF: 0.478 Hom.: 14289

Bravo AF: 0.418

Asia WGS AF: 0.373 AC: 1299 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	3.4
DANN	Benign	0.28
PhyloP100		-0.17
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: rs1061477; hg19: chr19-51360096;