1-14621424-T-C

Variant names:

• chr1-14621424-T-C
• rs11579756
• NM_201628.3:c.226+22201T>C

Variant summary

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

The NM_201628.3(KAZN):​c.226+22201T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.359 in 152,170 control chromosomes in the GnomAD database, including 11,328 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 (11328 hom., cov: 33)
• Consequence: KAZN NM_201628.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00900
• Publications: 5 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.576 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KAZN	NM_201628.3	c.226+22201T>C		intron_variant	Intron 1 of 14	ENST00000376030.7	NP_963922.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KAZN	ENST00000376030.7	c.226+22201T>C		intron_variant	Intron 1 of 14	5	NM_201628.3	ENSP00000365198.2
KAZN	ENST00000503743.5	c.226+22201T>C		intron_variant	Intron 2 of 8	1		ENSP00000426015.1
KAZN	ENST00000636203.1	c.490+22201T>C		intron_variant	Intron 3 of 16	5		ENSP00000490958.1
KAZN	ENST00000491547.1	n.520+22201T>C		intron_variant	Intron 1 of 6	2

Frequencies

GnomAD3 genomes AF: 0.358 AC: 54494 AN: 152052 Hom.: 11299 Cov.: 33

Gnomad AFR AF: 0.582

Gnomad AMI AF: 0.181

Gnomad AMR AF: 0.231

Gnomad ASJ AF: 0.372

Gnomad EAS AF: 0.334

Gnomad SAS AF: 0.340

Gnomad FIN AF: 0.250

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.274

Gnomad OTH AF: 0.337

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

GnomAD4 genome AF: 0.359 AC: 54565 AN: 152170 Hom.: 11328 Cov.: 33 AF XY: 0.355 AC XY: 26383 AN XY: 74392

African (AFR) AF: 0.583 AC: 24164 AN: 41474

American (AMR) AF: 0.230 AC: 3520 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.372 AC: 1290 AN: 3472

East Asian (EAS) AF: 0.334 AC: 1727 AN: 5174

South Asian (SAS) AF: 0.340 AC: 1644 AN: 4830

European-Finnish (FIN) AF: 0.250 AC: 2646 AN: 10592

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.274 AC: 18617 AN: 68018

Other (OTH) AF: 0.332 AC: 703 AN: 2116

Alfa AF: 0.299 Hom.: 28425

Bravo AF: 0.365

Asia WGS AF: 0.367 AC: 1277 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.0
DANN	Benign	0.45
PhyloP100		0.0090
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: rs11579756; hg19: chr1-14947920;