rs10492983

Variant names:

• chr1-14455488-G-A
• rs10492983
• ENST00000636203.1:c.250-143495G>A

Variant summary

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

The ENST00000636203.1(KAZN):​c.250-143495G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0256 in 152,298 control chromosomes in the GnomAD database, including 192 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 0.026 (192 hom., cov: 32)
• Consequence: KAZN ENST00000636203.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.480

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.165 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KAZN	XM_011541074.4	c.280-143495G>A		intron_variant	Intron 2 of 15		XP_011539376.1
KAZN	XM_005245795.6	c.280-143495G>A		intron_variant	Intron 2 of 16		XP_005245852.1
KAZN	XM_011541080.4	c.280-143495G>A		intron_variant	Intron 2 of 12		XP_011539382.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KAZN	ENST00000636203.1	c.250-143495G>A		intron_variant	Intron 2 of 16	5		ENSP00000490958.1

Frequencies

GnomAD3 genomes AF: 0.0256 AC: 3892 AN: 152180 Hom.: 190 Cov.: 32

Gnomad AFR AF: 0.00475

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0878

Gnomad ASJ AF: 0.0124

Gnomad EAS AF: 0.174

Gnomad SAS AF: 0.0429

Gnomad FIN AF: 0.0281

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0126

Gnomad OTH AF: 0.0229

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

GnomAD4 genome AF: 0.0256 AC: 3903 AN: 152298 Hom.: 192 Cov.: 32 AF XY: 0.0279 AC XY: 2076 AN XY: 74472

Gnomad4 AFR AF: 0.00474 AC: 0.00473877 AN: 0.00473877

Gnomad4 AMR AF: 0.0880 AC: 0.0880277 AN: 0.0880277

Gnomad4 ASJ AF: 0.0124 AC: 0.0123848 AN: 0.0123848

Gnomad4 EAS AF: 0.175 AC: 0.174545 AN: 0.174545

Gnomad4 SAS AF: 0.0432 AC: 0.0431714 AN: 0.0431714

Gnomad4 FIN AF: 0.0281 AC: 0.0280603 AN: 0.0280603

Gnomad4 NFE AF: 0.0126 AC: 0.0125974 AN: 0.0125974

Gnomad4 OTH AF: 0.0241 AC: 0.0241021 AN: 0.0241021

Alfa AF: 0.0251 Hom.: 48

Bravo AF: 0.0318

Asia WGS AF: 0.103 AC: 356 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.80
DANN	Benign	0.82

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10492983; hg19: chr1-14781984;