1-15013464-T-C

Variant names:

• chr1-15013464-T-C
• rs6429703
• NM_201628.3:c.419-21285T>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.419-21285T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.853 in 152,184 control chromosomes in the GnomAD database, including 55,478 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 0.85 (55478 hom., cov: 33)
• Consequence: KAZN NM_201628.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.708
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.864 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_201628.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KAZN	NM_201628.3	MANE Select	c.419-21285T>C		intron	N/A	NP_963922.2	Q674X7-1
	KAZN	NM_001437721.1		c.419-21285T>C		intron	N/A	NP_001424650.1
	KAZN	NM_015209.3		c.419-21285T>C		intron	N/A	NP_056024.1	Q674X7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KAZN	ENST00000376030.7	TSL:5 MANE Select	c.419-21285T>C		intron	N/A	ENSP00000365198.2	Q674X7-1
	KAZN	ENST00000503743.5	TSL:1	c.419-21285T>C		intron	N/A	ENSP00000426015.1	Q674X7-2
	KAZN	ENST00000361144.9	TSL:1	c.401-21285T>C		intron	N/A	ENSP00000354727.5	Q674X7-3

Frequencies

GnomAD3 genomes AF: 0.853 AC: 129764 AN: 152064 Hom.: 55436 Cov.: 33

Gnomad AFR AF: 0.831

Gnomad AMI AF: 0.932

Gnomad AMR AF: 0.819

Gnomad ASJ AF: 0.827

Gnomad EAS AF: 0.833

Gnomad SAS AF: 0.870

Gnomad FIN AF: 0.890

Gnomad MID AF: 0.823

Gnomad NFE AF: 0.869

Gnomad OTH AF: 0.858

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

GnomAD4 genome AF: 0.853 AC: 129864 AN: 152184 Hom.: 55478 Cov.: 33 AF XY: 0.855 AC XY: 63591 AN XY: 74406

African (AFR) AF: 0.831 AC: 34512 AN: 41510

American (AMR) AF: 0.819 AC: 12531 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.827 AC: 2870 AN: 3472

East Asian (EAS) AF: 0.833 AC: 4309 AN: 5170

South Asian (SAS) AF: 0.870 AC: 4195 AN: 4822

European-Finnish (FIN) AF: 0.890 AC: 9420 AN: 10588

Middle Eastern (MID) AF: 0.823 AC: 242 AN: 294

European-Non Finnish (NFE) AF: 0.869 AC: 59124 AN: 68006

Other (OTH) AF: 0.856 AC: 1811 AN: 2116

Alfa AF: 0.859 Hom.: 152596

Bravo AF: 0.847

Asia WGS AF: 0.858 AC: 2986 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.6
DANN	Benign	0.28
PhyloP100		-0.71
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: rs6429703; hg19: chr1-15339960;