19-50858179-C-T
Position:
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6BP7
The NM_001648.2(KLK3):c.357C>T(p.His119His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,614,108 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).
Frequency
Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000010 ( 0 hom. )
Consequence
KLK3
NM_001648.2 synonymous
NM_001648.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.56
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.56).
BP6
Variant 19-50858179-C-T is Benign according to our data. Variant chr19-50858179-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3350527.Status of the report is no_assertion_criteria_provided, 0 stars.
BP7
Synonymous conserved (PhyloP=-2.56 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
KLK3 | NM_001648.2 | c.357C>T | p.His119His | synonymous_variant | 3/5 | ENST00000326003.7 | NP_001639.1 | |
KLK3 | NM_001030047.1 | c.357C>T | p.His119His | synonymous_variant | 3/5 | NP_001025218.1 | ||
KLK3 | NM_001030048.1 | c.228C>T | p.His76His | synonymous_variant | 3/5 | NP_001025219.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152236Hom.: 0 Cov.: 32
GnomAD3 genomes
AF:
AC:
6
AN:
152236
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251354Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135850
GnomAD3 exomes
AF:
AC:
3
AN:
251354
Hom.:
AF XY:
AC XY:
3
AN XY:
135850
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000103 AC: 15AN: 1461872Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5AN XY: 727242
GnomAD4 exome
AF:
AC:
15
AN:
1461872
Hom.:
Cov.:
31
AF XY:
AC XY:
5
AN XY:
727242
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152236Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74374
GnomAD4 genome
AF:
AC:
6
AN:
152236
Hom.:
Cov.:
32
AF XY:
AC XY:
4
AN XY:
74374
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Bravo
AF:
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
KLK3-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | May 28, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at