NM_001648.2:c.116A>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001648.2(KLK3):​c.116A>G​(p.Gln39Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,254 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000014 ( 0 hom. )

Consequence

KLK3
NM_001648.2 missense

Scores

1
4
4

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.990
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 made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KLK3NM_001648.2 linkc.116A>G p.Gln39Arg missense_variant Exon 2 of 5 ENST00000326003.7 NP_001639.1 P07288-1Q546G3
KLK3NM_001030047.1 linkc.116A>G p.Gln39Arg missense_variant Exon 2 of 5 NP_001025218.1 P07288-2
KLK3NM_001030048.1 linkc.116A>G p.Gln39Arg missense_variant Exon 2 of 5 NP_001025219.1 P07288-3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
KLK3ENST00000326003.7 linkc.116A>G p.Gln39Arg missense_variant Exon 2 of 5 1 NM_001648.2 ENSP00000314151.1 P07288-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461254
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
726932
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.92
BayesDel_addAF
Uncertain
0.075
D
BayesDel_noAF
Uncertain
-0.070
CADD
Uncertain
24
DANN
Uncertain
0.99
Eigen
Benign
0.18
Eigen_PC
Benign
-0.065
FATHMM_MKL
Uncertain
0.86
D
M_CAP
Benign
0.027
D
ClinPred
0.89
D
GERP RS
1.0
La Branchor
0.41

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-51359565; API