chr19-50861013-A-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001648.2(KLK3):​c.*886A>G variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.777 in 151,932 control chromosomes in the GnomAD database, including 46,634 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 0.78 ( 46634 hom., cov: 30)

Consequence

KLK3
NM_001648.2 downstream_gene

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.649

Publications

12 publications found
Variant links:
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]

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.852 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KLK3NM_001648.2 linkc.*886A>G downstream_gene_variant ENST00000326003.7 NP_001639.1 P07288-1Q546G3
KLK3NM_001030047.1 linkc.*1397A>G downstream_gene_variant NP_001025218.1 P07288-2
KLK3NM_001030048.1 linkc.*886A>G downstream_gene_variant NP_001025219.1 P07288-3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
KLK3ENST00000326003.7 linkc.*886A>G downstream_gene_variant 1 NM_001648.2 ENSP00000314151.1 P07288-1
KLK3ENST00000422986.6 linkn.*1328A>G downstream_gene_variant 1 ENSP00000393628.2 A0A0B4J1X3
KLK3ENST00000601349.5 linkn.*249A>G downstream_gene_variant 1

Frequencies

GnomAD3 genomes
AF:
0.777
AC:
117955
AN:
151814
Hom.:
46612
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.657
Gnomad AMI
AF:
0.776
Gnomad AMR
AF:
0.767
Gnomad ASJ
AF:
0.812
Gnomad EAS
AF:
0.584
Gnomad SAS
AF:
0.669
Gnomad FIN
AF:
0.876
Gnomad MID
AF:
0.758
Gnomad NFE
AF:
0.857
Gnomad OTH
AF:
0.770
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.777
AC:
118026
AN:
151932
Hom.:
46634
Cov.:
30
AF XY:
0.774
AC XY:
57441
AN XY:
74260
show subpopulations
African (AFR)
AF:
0.657
AC:
27193
AN:
41388
American (AMR)
AF:
0.766
AC:
11702
AN:
15276
Ashkenazi Jewish (ASJ)
AF:
0.812
AC:
2816
AN:
3466
East Asian (EAS)
AF:
0.584
AC:
3010
AN:
5152
South Asian (SAS)
AF:
0.670
AC:
3227
AN:
4814
European-Finnish (FIN)
AF:
0.876
AC:
9272
AN:
10582
Middle Eastern (MID)
AF:
0.740
AC:
216
AN:
292
European-Non Finnish (NFE)
AF:
0.857
AC:
58263
AN:
67950
Other (OTH)
AF:
0.771
AC:
1621
AN:
2102
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.503
Heterozygous variant carriers
0
1275
2550
3825
5100
6375
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
858
1716
2574
3432
4290
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.823
Hom.:
37161
Bravo
AF:
0.761
Asia WGS
AF:
0.618
AC:
2152
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.90
CADD
Benign
4.6
DANN
Benign
0.83
PhyloP100
-0.65

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs2569735; hg19: chr19-51364269; API