chr1-15101742-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_201628.3(KAZN):c.1747G>A(p.Glu583Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000012 in 1,587,300 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000010 ( 0 hom. )
Consequence
KAZN
NM_201628.3 missense
NM_201628.3 missense
Scores
5
8
Clinical Significance
Conservation
PhyloP100: 4.50
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]
Genome browser will be placed here
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=0.2298736).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KAZN | NM_201628.3 | c.1747G>A | p.Glu583Lys | missense_variant | 11/15 | ENST00000376030.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KAZN | ENST00000376030.7 | c.1747G>A | p.Glu583Lys | missense_variant | 11/15 | 5 | NM_201628.3 | P2 | |
KAZN | ENST00000636203.1 | c.2011G>A | p.Glu671Lys | missense_variant | 13/17 | 5 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152186Hom.: 0 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
4
AN:
152186
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0000287 AC: 6AN: 208836Hom.: 0 AF XY: 0.0000270 AC XY: 3AN XY: 111000
GnomAD3 exomes
AF:
AC:
6
AN:
208836
Hom.:
AF XY:
AC XY:
3
AN XY:
111000
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000105 AC: 15AN: 1435114Hom.: 0 Cov.: 33 AF XY: 0.0000141 AC XY: 10AN XY: 710818
GnomAD4 exome
AF:
AC:
15
AN:
1435114
Hom.:
Cov.:
33
AF XY:
AC XY:
10
AN XY:
710818
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152186Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74352
GnomAD4 genome
?
AF:
AC:
4
AN:
152186
Hom.:
Cov.:
32
AF XY:
AC XY:
4
AN XY:
74352
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ESP6500AA
AF:
AC:
0
ESP6500EA
AF:
AC:
1
ExAC
?
AF:
AC:
3
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 | Aug 22, 2023 | The c.1747G>A (p.E583K) alteration is located in exon 11 (coding exon 11) of the KAZN gene. This alteration results from a G to A substitution at nucleotide position 1747, causing the glutamic acid (E) at amino acid position 583 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationTaster
Benign
D
PrimateAI
Uncertain
T
Polyphen
0.86
.;P
Vest4
0.64
MVP
0.51
MPC
0.90
ClinPred
T
GERP RS
Varity_R
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