chr19-50855373-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001648.2(KLK3):​c.46+372C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 258,464 control chromosomes in the GnomAD database, including 10,063 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 0.24 ( 5336 hom., cov: 31)
Exomes 𝑓: 0.28 ( 4727 hom. )

Consequence

KLK3
NM_001648.2 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.56
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 Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.92).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.418 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
KLK3NM_001648.2 linkuse as main transcriptc.46+372C>T intron_variant ENST00000326003.7 NP_001639.1 P07288-1Q546G3
KLK3NM_001030047.1 linkuse as main transcriptc.46+372C>T intron_variant NP_001025218.1 P07288-2
KLK3NM_001030048.1 linkuse as main transcriptc.46+372C>T intron_variant NP_001025219.1 P07288-3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
KLK3ENST00000326003.7 linkuse as main transcriptc.46+372C>T intron_variant 1 NM_001648.2 ENSP00000314151.1 P07288-1

Frequencies

GnomAD3 genomes
AF:
0.241
AC:
36581
AN:
151886
Hom.:
5329
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0906
Gnomad AMI
AF:
0.258
Gnomad AMR
AF:
0.331
Gnomad ASJ
AF:
0.232
Gnomad EAS
AF:
0.434
Gnomad SAS
AF:
0.171
Gnomad FIN
AF:
0.382
Gnomad MID
AF:
0.184
Gnomad NFE
AF:
0.281
Gnomad OTH
AF:
0.224
GnomAD4 exome
AF:
0.276
AC:
29341
AN:
106460
Hom.:
4727
Cov.:
0
AF XY:
0.270
AC XY:
14940
AN XY:
55388
show subpopulations
Gnomad4 AFR exome
AF:
0.0813
Gnomad4 AMR exome
AF:
0.374
Gnomad4 ASJ exome
AF:
0.231
Gnomad4 EAS exome
AF:
0.454
Gnomad4 SAS exome
AF:
0.175
Gnomad4 FIN exome
AF:
0.376
Gnomad4 NFE exome
AF:
0.275
Gnomad4 OTH exome
AF:
0.261
GnomAD4 genome
AF:
0.241
AC:
36602
AN:
152004
Hom.:
5336
Cov.:
31
AF XY:
0.245
AC XY:
18170
AN XY:
74306
show subpopulations
Gnomad4 AFR
AF:
0.0905
Gnomad4 AMR
AF:
0.331
Gnomad4 ASJ
AF:
0.232
Gnomad4 EAS
AF:
0.433
Gnomad4 SAS
AF:
0.171
Gnomad4 FIN
AF:
0.382
Gnomad4 NFE
AF:
0.281
Gnomad4 OTH
AF:
0.232
Alfa
AF:
0.270
Hom.:
1487
Bravo
AF:
0.232
Asia WGS
AF:
0.295
AC:
1025
AN:
3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.92
CADD
Benign
0.11
DANN
Benign
0.53

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1053972; hg19: chr19-51358629; API