NM_201628.3:c.227-28755G>A

Variant names:

• chr1-14931929-G-A
• rs10927583
• NM_201628.3:c.227-28755G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_201628.3(KAZN):​c.227-28755G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 151,960 control chromosomes in the GnomAD database, including 12,071 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.36 (12071 hom., cov: 32)
• Consequence: KAZN NM_201628.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.96
• Publications: 4 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.597 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KAZN	NM_201628.3	MANE Select	c.227-28755G>A		intron	N/A	NP_963922.2
	KAZN	NM_001437721.1		c.227-28755G>A		intron	N/A	NP_001424650.1
	KAZN	NM_015209.3		c.227-28755G>A		intron	N/A	NP_056024.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KAZN	ENST00000376030.7	TSL:5 MANE Select	c.227-28755G>A		intron	N/A	ENSP00000365198.2
	KAZN	ENST00000503743.5	TSL:1	c.227-28755G>A		intron	N/A	ENSP00000426015.1
	KAZN	ENST00000361144.9	TSL:1	c.208+7357G>A		intron	N/A	ENSP00000354727.5

Frequencies

GnomAD3 genomes AF: 0.364 AC: 55205 AN: 151842 Hom.: 12026 Cov.: 32

Gnomad AFR AF: 0.603

Gnomad AMI AF: 0.360

Gnomad AMR AF: 0.281

Gnomad ASJ AF: 0.288

Gnomad EAS AF: 0.472

Gnomad SAS AF: 0.462

Gnomad FIN AF: 0.167

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.256

Gnomad OTH AF: 0.362

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.364 AC: 55314 AN: 151960 Hom.: 12071 Cov.: 32 AF XY: 0.360 AC XY: 26717 AN XY: 74282

African (AFR) AF: 0.603 AC: 25013 AN: 41464

American (AMR) AF: 0.280 AC: 4274 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.288 AC: 999 AN: 3468

East Asian (EAS) AF: 0.473 AC: 2431 AN: 5144

South Asian (SAS) AF: 0.463 AC: 2231 AN: 4816

European-Finnish (FIN) AF: 0.167 AC: 1762 AN: 10556

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.256 AC: 17415 AN: 67954

Other (OTH) AF: 0.366 AC: 771 AN: 2106

Alfa AF: 0.289 Hom.: 26976

Bravo AF: 0.380

Asia WGS AF: 0.459 AC: 1597 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.16
DANN	Benign	0.71
PhyloP100		-3.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10927583; hg19: chr1-15258425;