19-50907030-G-T
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP2
The NM_004917.5(KLK4):c.669C>A(p.Phe223Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: not found (cov: 32)
Consequence
KLK4
NM_004917.5 missense
NM_004917.5 missense
Scores
1
4
11
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.495
Publications
0 publications found
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 2A1Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
- amelogenesis imperfecta type 2Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 1 curated pathogenic missense variants (we use a threshold of 10). The gene has 0 curated benign missense variants. Gene score misZ: 0.031208 (below the threshold of 3.09). Trascript score misZ: -0.079907 (below the threshold of 3.09). GenCC associations: The gene is linked to amelogenesis imperfecta type 2, amelogenesis imperfecta type 2A1.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_004917.5. You can select a different transcript below to see updated ACMG assignments.
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| KLK4 | TSL:1 MANE Select | c.669C>A | p.Phe223Leu | missense | Exon 6 of 6 | ENSP00000326159.1 | A0A0C4DFQ5 | ||
| KLK4 | TSL:1 | c.*52C>A | 3_prime_UTR | Exon 3 of 3 | ENSP00000399448.2 | Q9Y5K2-2 | |||
| KLK4 | TSL:1 | n.*164C>A | non_coding_transcript_exon | Exon 5 of 5 | ENSP00000469963.1 | M0QYN5 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
DANN
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
M_CAP
Benign
D
MetaRNN
Uncertain
T
MetaSVM
Benign
T
PhyloP100
PrimateAI
Benign
T
PROVEAN
Uncertain
D
REVEL
Uncertain
Sift
Benign
T
Sift4G
Uncertain
D
Vest4
MutPred
Loss of methylation at K225 (P = 0.1162)
MVP
MPC
ClinPred
T
GERP RS
gMVP
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
Publications
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