rs34750956

Variant names:

• chr19-50858740-C-T
• rs34750956
• ENST00000593997.5:c.*91C>T

Variant summary

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

The ENST00000593997.5(KLK3):​c.*91C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 806,578 control chromosomes in the GnomAD database, including 5,186 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 0.10 (831 hom., cov: 32)
  • Exomes 𝑓: 0.11 (4355 hom.)
• Consequence: KLK3 ENST00000593997.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.798
• Publications: 4 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.119 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLK3	NM_001648.2	c.630+145C>T		intron_variant	Intron 4 of 4	ENST00000326003.7	NP_001639.1
KLK3	NM_001030047.1	c.630+145C>T		intron_variant	Intron 4 of 4		NP_001025218.1
KLK3	NM_001030048.1	c.501+145C>T		intron_variant	Intron 4 of 4		NP_001025219.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLK3	ENST00000326003.7	c.630+145C>T		intron_variant	Intron 4 of 4	1	NM_001648.2	ENSP00000314151.1

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15535 AN: 152080 Hom.: 832 Cov.: 32

Gnomad AFR AF: 0.0770

Gnomad AMI AF: 0.178

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.194

Gnomad EAS AF: 0.0705

Gnomad SAS AF: 0.0847

Gnomad FIN AF: 0.0546

Gnomad MID AF: 0.150

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.124

GnomAD4 exome AF: 0.110 AC: 72169 AN: 654378 Hom.: 4355 Cov.: 9 AF XY: 0.110 AC XY: 37417 AN XY: 338650

African (AFR) AF: 0.0752 AC: 1249 AN: 16606

American (AMR) AF: 0.0878 AC: 2019 AN: 22988

Ashkenazi Jewish (ASJ) AF: 0.198 AC: 3071 AN: 15528

East Asian (EAS) AF: 0.0681 AC: 2259 AN: 33152

South Asian (SAS) AF: 0.0850 AC: 4603 AN: 54128

European-Finnish (FIN) AF: 0.0586 AC: 2153 AN: 36720

Middle Eastern (MID) AF: 0.203 AC: 760 AN: 3750

European-Non Finnish (NFE) AF: 0.119 AC: 52152 AN: 438418

Other (OTH) AF: 0.118 AC: 3903 AN: 33088

GnomAD4 genome AF: 0.102 AC: 15539 AN: 152200 Hom.: 831 Cov.: 32 AF XY: 0.0991 AC XY: 7375 AN XY: 74412

African (AFR) AF: 0.0769 AC: 3192 AN: 41520

American (AMR) AF: 0.105 AC: 1604 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.194 AC: 673 AN: 3470

East Asian (EAS) AF: 0.0707 AC: 365 AN: 5162

South Asian (SAS) AF: 0.0859 AC: 414 AN: 4822

European-Finnish (FIN) AF: 0.0546 AC: 580 AN: 10616

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.121 AC: 8248 AN: 68006

Other (OTH) AF: 0.123 AC: 259 AN: 2110

Alfa AF: 0.104 Hom.: 214

Bravo AF: 0.106

Asia WGS AF: 0.0700 AC: 243 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.5
DANN	Benign	0.49
PhyloP100		-0.80
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs34750956; hg19: chr19-51361996;