chr1-15056259-C-G
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_201628.3(KAZN):āc.895C>Gā(p.Pro299Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000559 in 1,608,724 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.0000066 ( 0 hom., cov: 33)
Exomes š: 0.0000055 ( 0 hom. )
Consequence
KAZN
NM_201628.3 missense
NM_201628.3 missense
Scores
3
16
Clinical Significance
Conservation
PhyloP100: 4.25
Genes affected
KAZN (HGNC:29173): (kazrin, periplakin interacting protein) This gene encodes a protein that plays a role in desmosome assembly, cell adhesion, cytoskeletal organization, and epidermal differentiation. This protein co-localizes with desmoplakin and the cytolinker protein periplakin. In general, this protein localizes to the nucleus, desmosomes, cell membrane, and cortical actin-based structures. Some isoforms of this protein also associate with microtubules. Alternative splicing results in multiple transcript variants encoding distinct isoforms. Additional splice variants have been described but their biological validity has not been verified. [provided by RefSeq, Aug 2011]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.12316126).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
KAZN | NM_201628.3 | c.895C>G | p.Pro299Ala | missense_variant | 5/15 | ENST00000376030.7 | NP_963922.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
KAZN | ENST00000376030.7 | c.895C>G | p.Pro299Ala | missense_variant | 5/15 | 5 | NM_201628.3 | ENSP00000365198.2 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152212Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00000802 AC: 2AN: 249302Hom.: 0 AF XY: 0.00000741 AC XY: 1AN XY: 134920
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GnomAD4 exome AF: 0.00000549 AC: 8AN: 1456512Hom.: 0 Cov.: 31 AF XY: 0.00000553 AC XY: 4AN XY: 723334
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152212Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74350
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 23, 2023 | The c.895C>G (p.P299A) alteration is located in exon 5 (coding exon 5) of the KAZN gene. This alteration results from a C to G substitution at nucleotide position 895, causing the proline (P) at amino acid position 299 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
.;T;.;.;.;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D;D;.
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
.;N;N;.;.;.
MutationTaster
Benign
N;N;N;N;N;N
PrimateAI
Uncertain
T
PROVEAN
Benign
.;N;N;N;N;N
REVEL
Benign
Sift
Benign
.;T;T;T;T;T
Sift4G
Benign
.;T;T;T;T;T
Polyphen
0.037, 0.0, 0.0010
.;B;B;B;B;B
Vest4
0.22, 0.29, 0.28, 0.29, 0.29
MVP
0.24
MPC
0.72
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at