19-50855432-C-T

Variant names:

• chr19-50855432-C-T
• rs2292185
• ENST00000601349.5:n.518C>T

Variant summary

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

The ENST00000601349.5(KLK3):​n.518C>T 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 0.38 in 169,296 control chromosomes in the GnomAD database, including 12,717 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 0.38 (11440 hom., cov: 31)
  • Exomes 𝑓: 0.36 (1277 hom.)
• Consequence: KLK3 ENST00000601349.5 non_coding_transcript_exon
• Scores: Splicing: ADA: 0.00005103
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.599
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.492 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLK3	NM_001648.2	c.46+431C>T		intron_variant	Intron 1 of 4	ENST00000326003.7	NP_001639.1
KLK3	NM_001030047.1	c.46+431C>T		intron_variant	Intron 1 of 4		NP_001025218.1
KLK3	NM_001030048.1	c.46+431C>T		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+431C>T		intron_variant	Intron 1 of 4	1	NM_001648.2	ENSP00000314151.1

Frequencies

GnomAD3 genomes AF: 0.383 AC: 58062 AN: 151748 Hom.: 11427 Cov.: 31

Gnomad AFR AF: 0.362

Gnomad AMI AF: 0.438

Gnomad AMR AF: 0.441

Gnomad ASJ AF: 0.333

Gnomad EAS AF: 0.509

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.431

Gnomad MID AF: 0.303

Gnomad NFE AF: 0.379

Gnomad OTH AF: 0.372

GnomAD4 exome AF: 0.359 AC: 6260 AN: 17428 Hom.: 1277 Cov.: 0 AF XY: 0.354 AC XY: 3276 AN XY: 9256

African (AFR) AF: 0.364 AC: 150 AN: 412

American (AMR) AF: 0.446 AC: 859 AN: 1924

Ashkenazi Jewish (ASJ) AF: 0.318 AC: 147 AN: 462

East Asian (EAS) AF: 0.514 AC: 362 AN: 704

South Asian (SAS) AF: 0.197 AC: 305 AN: 1548

European-Finnish (FIN) AF: 0.428 AC: 243 AN: 568

Middle Eastern (MID) AF: 0.173 AC: 9 AN: 52

European-Non Finnish (NFE) AF: 0.357 AC: 3867 AN: 10824

Other (OTH) AF: 0.340 AC: 318 AN: 934

GnomAD4 genome AF: 0.383 AC: 58111 AN: 151868 Hom.: 11440 Cov.: 31 AF XY: 0.383 AC XY: 28403 AN XY: 74206

African (AFR) AF: 0.362 AC: 14996 AN: 41390

American (AMR) AF: 0.441 AC: 6734 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.333 AC: 1155 AN: 3470

East Asian (EAS) AF: 0.508 AC: 2609 AN: 5132

South Asian (SAS) AF: 0.220 AC: 1060 AN: 4828

European-Finnish (FIN) AF: 0.431 AC: 4545 AN: 10552

Middle Eastern (MID) AF: 0.288 AC: 84 AN: 292

European-Non Finnish (NFE) AF: 0.379 AC: 25737 AN: 67932

Other (OTH) AF: 0.378 AC: 796 AN: 2106

Alfa AF: 0.373 Hom.: 40242

Bravo AF: 0.387

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	5.1
DANN	Benign	0.25
PhyloP100		-0.60
PromoterAI		-0.0053	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000051
dbscSNV1_RF	Benign	0.0
SpliceAI score (max)		0.030		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: rs2292185; hg19: chr19-51358688;