Variant chr1-14599136-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_201628.3(KAZN):c.139G>C(p.Gly47Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000767 in 1,303,314 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: not found (cov: 32)

Exomes 𝑓: 7.7e-7 ( 0 hom. )

Consequence

KAZN
NM_201628.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.88

Variant links:

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]

KAZN links:

KAZN (HGNC:):

KAZN links:

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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=0.17518726).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KAZN	NM_201628.3 linkuse as main transcript	c.139G>C	p.Gly47Arg	missense_variant	1/15	ENST00000376030.7	NP_963922.2	Q674X7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
KAZN	ENST00000376030.7 linkuse as main transcript	c.139G>C	p.Gly47Arg	missense_variant	1/15	5	NM_201628.3	ENSP00000365198.2	Q674X7-1
KAZN	ENST00000503743.5 linkuse as main transcript	c.139G>C	p.Gly47Arg	missense_variant	2/9	1		ENSP00000426015.1	Q674X7-2
KAZN	ENST00000636203.1 linkuse as main transcript	c.403G>C	p.Gly135Arg	missense_variant	3/17	5		ENSP00000490958.1	A0A1B0GWK2
KAZN	ENST00000491547.1 linkuse as main transcript	n.433G>C		non_coding_transcript_exon_variant	1/7	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000866

AC:

AN:

115478

Hom.:

AF XY:

0.0000149

AC XY:

AN XY:

67210

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000108

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.67e-7

AC:

AN:

1303314

Hom.:

Cov.:

AF XY:

0.00000155

AC XY:

AN XY:

643962

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000543

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000897

AC:

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

Jun 28, 2023

The c.139G>C (p.G47R) alteration is located in exon 1 (coding exon 1) of the KAZN gene. This alteration results from a G to C substitution at nucleotide position 139, causing the glycine (G) at amino acid position 47 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.30

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0064

.;T;.

Eigen

Benign

0.060

Eigen_PC

Benign

0.071

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.43

T;T;T

M_CAP

Uncertain

0.14

MetaRNN

Benign

0.18

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.34

.;N;N

MutationTaster

Benign

0.99

N;N;N

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

-0.11

.;N;N

REVEL

Benign

0.075

Sift

Uncertain

0.029

.;D;T

Sift4G

Benign

0.15

.;T;D

Polyphen

0.82, 0.90

.;P;P

Vest4

0.21, 0.26

MutPred

0.26

.;Gain of methylation at G47 (P = 0.0184);Gain of methylation at G47 (P = 0.0184);

MVP

0.22

MPC

1.9

ClinPred

0.41

GERP RS

2.5

Varity_R

0.083

gMVP

0.095

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over