chr1-15112540-G-A

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_201628.3(KAZN):c.2162G>A(p.Arg721Gln) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000739 in 1,556,294 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R721W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000062 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000075 ( 0 hom. )

Consequence

KAZN
NM_201628.3 missense, splice_region

Scores

Splicing: ADA: 0.4505

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.87

Publications

0 publications found

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:

TMEM51-AS1 (HGNC:26301): (TMEM51 antisense RNA 1)

TMEM51-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.22839895).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_201628.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KAZN	NM_201628.3	MANE Select	c.2162G>A	p.Arg721Gln	missense splice_region	Exon 14 of 15	NP_963922.2	Q674X7-1
	TMEM51-AS1	NR_027136.1		n.6254C>T		non_coding_transcript_exon	Exon 5 of 5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KAZN	ENST00000376030.7	TSL:5 MANE Select	c.2162G>A	p.Arg721Gln	missense splice_region	Exon 14 of 15	ENSP00000365198.2	Q674X7-1
TMEM51-AS1	ENST00000404665.4	TSL:1	n.6248C>T		non_coding_transcript_exon	Exon 5 of 5
KAZN	ENST00000636203.1	TSL:5	c.2426G>A	p.Arg809Gln	missense splice_region	Exon 16 of 17	ENSP00000490958.1	A0A1B0GWK2

Frequencies

GnomAD3 genomes

AF:

0.0000619

AC:

AN:

129274

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000292

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000775

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000102

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000278

AC:

AN:

216040

AF XY:

0.00000859

show subpopulations

Gnomad AFR exome

AF:

0.0000759

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000624

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000416

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000750

AC:

107

AN:

1427020

Hom.:

Cov.:

AF XY:

0.0000764

AC XY:

AN XY:

706678

show subpopulations

African (AFR)

AF:

0.0000612

AC:

AN:

32664

American (AMR)

AF:

0.0000239

AC:

AN:

41848

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25308

East Asian (EAS)

AF:

0.0000259

AC:

AN:

38658

South Asian (SAS)

AF:

0.0000122

AC:

AN:

81884

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51898

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5660

European-Non Finnish (NFE)

AF:

0.0000890

AC:

AN:

1090314

Other (OTH)

AF:

0.0000851

AC:

AN:

58786

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000619

AC:

AN:

129274

Hom.:

Cov.:

AF XY:

0.0000634

AC XY:

AN XY:

63044

show subpopulations

African (AFR)

AF:

0.0000292

AC:

AN:

34198

American (AMR)

AF:

0.0000775

AC:

AN:

12902

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2994

East Asian (EAS)

AF:

0.00

AC:

AN:

4760

South Asian (SAS)

AF:

0.00

AC:

AN:

4104

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8734

Middle Eastern (MID)

AF:

0.00

AC:

AN:

254

European-Non Finnish (NFE)

AF:

0.000102

AC:

AN:

58816

Other (OTH)

AF:

0.00

AC:

AN:

1758

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000676

Hom.:

Bravo

AF:

0.0000604

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00000826

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.42

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0061

Eigen

Uncertain

0.40

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Benign

0.71

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.011

MetaRNN

Benign

0.23

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

PhyloP100

4.9

PrimateAI

Benign

0.42

PROVEAN

Benign

0.040

REVEL

Benign

0.15

Sift

Uncertain

0.010

Sift4G

Benign

0.14

Polyphen

0.99

Vest4

0.44

MVP

0.40

MPC

0.12

ClinPred

0.18

GERP RS

5.6

Varity_R

0.14

gMVP

0.40

Mutation Taster

=87/13

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.45

dbscSNV1_RF

Benign

0.38

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over