1-13916277-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000636203.1(KAZN):c.91+22521C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0732 in 152,152 control chromosomes in the GnomAD database, including 485 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 0.073 (485 hom., cov: 32)
• Consequence: KAZN ENST00000636203.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.181

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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KAZN	XM_005245795.6	c.121+22521C>T		intron_variant
KAZN	XM_011541074.4	c.121+22521C>T		intron_variant
KAZN	XM_011541080.4	c.121+22521C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KAZN	ENST00000636203.1	c.91+22521C>T		intron_variant		5		A2
KAZN	ENST00000636564.1	c.91+22521C>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0731 AC: 11120 AN: 152034 Hom.: 484 Cov.: 32

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.0338

Gnomad ASJ AF: 0.0406

Gnomad EAS AF: 0.139

Gnomad SAS AF: 0.0855

Gnomad FIN AF: 0.0562

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0617

Gnomad OTH AF: 0.0532

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

GnomAD4 genome AF: 0.0732 AC: 11135 AN: 152152 Hom.: 485 Cov.: 32 AF XY: 0.0717 AC XY: 5331 AN XY: 74394

Gnomad4 AFR AF: 0.106

Gnomad4 AMR AF: 0.0337

Gnomad4 ASJ AF: 0.0406

Gnomad4 EAS AF: 0.139

Gnomad4 SAS AF: 0.0860

Gnomad4 FIN AF: 0.0562

Gnomad4 NFE AF: 0.0617

Gnomad4 OTH AF: 0.0564

Alfa AF: 0.0564 Hom.: 362

Bravo AF: 0.0717

Asia WGS AF: 0.125 AC: 435 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	5.1
Dann	Benign	0.65

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs16853148; hg19: chr1-14242772;