1-15103407-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_201628.3(KAZN):c.1828G>A(p.Val610Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000122 in 1,552,380 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 0.000039 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000093 ( 0 hom. )
Consequence
KAZN
NM_201628.3 missense
NM_201628.3 missense
Scores
8
5
Clinical Significance
Conservation
PhyloP100: 1.28
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 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.2745511).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KAZN | NM_201628.3 | c.1828G>A | p.Val610Met | missense_variant | 12/15 | ENST00000376030.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KAZN | ENST00000376030.7 | c.1828G>A | p.Val610Met | missense_variant | 12/15 | 5 | NM_201628.3 | P2 | |
KAZN | ENST00000636203.1 | c.2092G>A | p.Val698Met | missense_variant | 14/17 | 5 | A2 |
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152218Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000622 AC: 1AN: 160684Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 84436
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GnomAD4 exome AF: 0.00000928 AC: 13AN: 1400162Hom.: 0 Cov.: 31 AF XY: 0.00000434 AC XY: 3AN XY: 690650
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GnomAD4 genome AF: 0.0000394 AC: 6AN: 152218Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74368
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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 | Sep 14, 2021 | The c.1828G>A (p.V610M) alteration is located in exon 12 (coding exon 12) of the KAZN gene. This alteration results from a G to A substitution at nucleotide position 1828, causing the valine (V) at amino acid position 610 to be replaced by a methionine (M). 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
Uncertain
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T
MetaSVM
Uncertain
T
MutationTaster
Benign
N
PrimateAI
Uncertain
T
Polyphen
0.99
.;D
Vest4
0.41
MutPred
0.50
.;Gain of MoRF binding (P = 0.095);
MVP
0.73
MPC
1.5
ClinPred
D
GERP RS
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