rs10927583

Positions:

• chr1-14931929-G-A
• chr1-14931929-G-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KAZN	NM_201628.3	c.227-28755G>A		intron_variant		ENST00000376030.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KAZN	ENST00000376030.7	c.227-28755G>A		intron_variant		5	NM_201628.3	P2

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

Gnomad4 AFR AF: 0.603

Gnomad4 AMR AF: 0.280

Gnomad4 ASJ AF: 0.288

Gnomad4 EAS AF: 0.473

Gnomad4 SAS AF: 0.463

Gnomad4 FIN AF: 0.167

Gnomad4 NFE AF: 0.256

Gnomad4 OTH AF: 0.366

Alfa AF: 0.270 Hom.: 9532

Bravo AF: 0.380

Asia WGS AF: 0.459 AC: 1597 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.16
DANN	Benign	0.71

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

Other links and lift over

dbSNP: rs10927583; hg19: chr1-15258425;