19-50855215-C-G

Variant names:

• chr19-50855215-C-G
• rs266880
• ENST00000596185.5:n.260C>G

Variant summary

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

The ENST00000596185.5(KLK3):​n.260C>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.447 in 568,230 control chromosomes in the GnomAD database, including 59,414 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 0.46 (16962 hom., cov: 29)
  • Exomes 𝑓: 0.44 (42452 hom.)
• Consequence: KLK3 ENST00000596185.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.316
• Publications: 6 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.521 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLK3	NM_001648.2	c.46+214C>G		intron_variant	Intron 1 of 4	ENST00000326003.7	NP_001639.1
KLK3	NM_001030047.1	c.46+214C>G		intron_variant	Intron 1 of 4		NP_001025218.1
KLK3	NM_001030048.1	c.46+214C>G		intron_variant	Intron 1 of 4		NP_001025219.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLK3	ENST00000326003.7	c.46+214C>G		intron_variant	Intron 1 of 4	1	NM_001648.2	ENSP00000314151.1

Frequencies

GnomAD3 genomes AF: 0.464 AC: 70424 AN: 151668 Hom.: 16955 Cov.: 29

Gnomad AFR AF: 0.527

Gnomad AMI AF: 0.345

Gnomad AMR AF: 0.355

Gnomad ASJ AF: 0.428

Gnomad EAS AF: 0.161

Gnomad SAS AF: 0.386

Gnomad FIN AF: 0.503

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.478

Gnomad OTH AF: 0.449

GnomAD2 exomes AF: 0.388 AC: 17806 AN: 45858 AF XY: 0.388

Gnomad AFR exome AF: 0.515

Gnomad AMR exome AF: 0.296

Gnomad ASJ exome AF: 0.391

Gnomad EAS exome AF: 0.153

Gnomad FIN exome AF: 0.515

Gnomad NFE exome AF: 0.478

Gnomad OTH exome AF: 0.418

GnomAD4 exome AF: 0.440 AC: 183280 AN: 416446 Hom.: 42452 Cov.: 4 AF XY: 0.439 AC XY: 96083 AN XY: 218950

African (AFR) AF: 0.521 AC: 5916 AN: 11346

American (AMR) AF: 0.295 AC: 5171 AN: 17504

Ashkenazi Jewish (ASJ) AF: 0.432 AC: 5512 AN: 12758

East Asian (EAS) AF: 0.188 AC: 5430 AN: 28928

South Asian (SAS) AF: 0.399 AC: 15982 AN: 40056

European-Finnish (FIN) AF: 0.501 AC: 14355 AN: 28636

Middle Eastern (MID) AF: 0.463 AC: 850 AN: 1836

European-Non Finnish (NFE) AF: 0.475 AC: 119223 AN: 251102

Other (OTH) AF: 0.446 AC: 10841 AN: 24280

GnomAD4 genome AF: 0.464 AC: 70459 AN: 151784 Hom.: 16962 Cov.: 29 AF XY: 0.461 AC XY: 34227 AN XY: 74176

African (AFR) AF: 0.527 AC: 21770 AN: 41344

American (AMR) AF: 0.354 AC: 5398 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.428 AC: 1485 AN: 3468

East Asian (EAS) AF: 0.162 AC: 837 AN: 5154

South Asian (SAS) AF: 0.386 AC: 1859 AN: 4814

European-Finnish (FIN) AF: 0.503 AC: 5290 AN: 10526

Middle Eastern (MID) AF: 0.439 AC: 129 AN: 294

European-Non Finnish (NFE) AF: 0.478 AC: 32442 AN: 67920

Other (OTH) AF: 0.444 AC: 936 AN: 2106

Alfa AF: 0.361 Hom.: 1245

Bravo AF: 0.453

Asia WGS AF: 0.281 AC: 978 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.0
DANN	Benign	0.36
PhyloP100		-0.32
PromoterAI		0.084	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs266880; hg19: chr19-51358471; COSMIC: COSV58101900; COSMIC: COSV58101900;