19-50909059-A-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_004917.5(KLK4):​c.224+193T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000754 in 1,326,400 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 30)
Exomes 𝑓: 7.5e-7 ( 0 hom. )

Consequence

KLK4
NM_004917.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.43

Publications

0 publications found
Variant links:
Genes affected
KLK4 (HGNC:6365): (kallikrein related peptidase 4) 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. This gene is one of the fifteen kallikrein subfamily members located in a cluster on chromosome 19. In some tissues its expression is hormonally regulated. The expression pattern of a similar mouse protein in murine developing teeth supports a role for the protein in the degradation of enamel proteins. Several transcript variants encoding different proteins have been found for this gene. [provided by RefSeq, Dec 2014]
KLK4 Gene-Disease associations (from GenCC):
  • amelogenesis imperfecta type 2A1
    Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
  • amelogenesis imperfecta type 2
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.96).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KLK4NM_004917.5 linkc.224+193T>A intron_variant Intron 3 of 5 ENST00000324041.6 NP_004908.4 Q9Y5K2A0A0C4DFQ5
KLK4NM_001302961.2 linkc.-62+181T>A intron_variant Intron 2 of 4 NP_001289890.1 Q9Y5K2Q5BQA0
KLK4NR_126566.2 linkn.217+181T>A intron_variant Intron 2 of 4
KLK4XM_011527545.4 linkc.224+193T>A intron_variant Intron 2 of 3 XP_011525847.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
KLK4ENST00000324041.6 linkc.224+193T>A intron_variant Intron 3 of 5 1 NM_004917.5 ENSP00000326159.1 A0A0C4DFQ5

Frequencies

GnomAD3 genomes
Cov.:
30
GnomAD4 exome
AF:
7.54e-7
AC:
1
AN:
1326400
Hom.:
0
Cov.:
40
AF XY:
0.00
AC XY:
0
AN XY:
646626
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
30312
American (AMR)
AF:
0.00
AC:
0
AN:
30846
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
21172
East Asian (EAS)
AF:
0.0000283
AC:
1
AN:
35302
South Asian (SAS)
AF:
0.00
AC:
0
AN:
68914
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
32010
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
3764
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1048832
Other (OTH)
AF:
0.00
AC:
0
AN:
55248
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.96
CADD
Benign
0.45
DANN
Benign
0.55
PhyloP100
-3.4
PromoterAI
-0.0052
Neutral

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

Publications

Other links and lift over

dbSNP: rs2242670; hg19: chr19-51412315; API