rs10489143

Variant names:

• chr1-14169400-C-G
• rs10489143
• ENST00000636203.1:c.92-11035C>G

Variant summary

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

The ENST00000636203.1(KAZN):​c.92-11035C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 152,148 control chromosomes in the GnomAD database, including 1,112 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 0.11 (1112 hom., cov: 32)
• Consequence: KAZN ENST00000636203.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.153
• Publications: 2 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.315 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KAZN	XM_011541074.4	c.122-11035C>G		intron_variant	Intron 1 of 15		XP_011539376.1
KAZN	XM_005245795.6	c.122-11035C>G		intron_variant	Intron 1 of 16		XP_005245852.1
KAZN	XM_011541080.4	c.122-11035C>G		intron_variant	Intron 1 of 12		XP_011539382.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KAZN	ENST00000636203.1	c.92-11035C>G		intron_variant	Intron 1 of 16	5		ENSP00000490958.1
KAZN	ENST00000636564.1	c.92-11035C>G		intron_variant	Intron 1 of 2	5		ENSP00000489835.1

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17395 AN: 152030 Hom.: 1110 Cov.: 32

Gnomad AFR AF: 0.0916

Gnomad AMI AF: 0.0614

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.328

Gnomad SAS AF: 0.0454

Gnomad FIN AF: 0.110

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.125

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

GnomAD4 genome AF: 0.114 AC: 17414 AN: 152148 Hom.: 1112 Cov.: 32 AF XY: 0.119 AC XY: 8829 AN XY: 74388

African (AFR) AF: 0.0917 AC: 3809 AN: 41526

American (AMR) AF: 0.171 AC: 2617 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.109 AC: 378 AN: 3472

East Asian (EAS) AF: 0.328 AC: 1684 AN: 5140

South Asian (SAS) AF: 0.0453 AC: 218 AN: 4816

European-Finnish (FIN) AF: 0.110 AC: 1170 AN: 10600

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.106 AC: 7177 AN: 68012

Other (OTH) AF: 0.125 AC: 264 AN: 2112

Alfa AF: 0.107 Hom.: 123

Bravo AF: 0.122

Asia WGS AF: 0.162 AC: 563 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.2
DANN	Benign	0.66
PhyloP100		0.15

Splicing

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

Other links and lift over

dbSNP: rs10489143; hg19: chr1-14495895;