1-14683324-T-C

Variant names:

• chr1-14683324-T-C
• rs1883661
• NM_201628.3:c.226+84101T>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+84101T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.534 in 152,018 control chromosomes in the GnomAD database, including 21,713 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 0.53 (21713 hom., cov: 32)
• Consequence: KAZN NM_201628.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.639
• Publications: 3 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.617 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KAZN	NM_201628.3	c.226+84101T>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+84101T>C		intron_variant	Intron 1 of 14	5	NM_201628.3	ENSP00000365198.2
KAZN	ENST00000503743.5	c.226+84101T>C		intron_variant	Intron 2 of 8	1		ENSP00000426015.1
KAZN	ENST00000636203.1	c.490+84101T>C		intron_variant	Intron 3 of 16	5		ENSP00000490958.1
KAZN	ENST00000491547.1	n.520+84101T>C		intron_variant	Intron 1 of 6	2

Frequencies

GnomAD3 genomes AF: 0.533 AC: 81035 AN: 151896 Hom.: 21689 Cov.: 32

Gnomad AFR AF: 0.542

Gnomad AMI AF: 0.630

Gnomad AMR AF: 0.434

Gnomad ASJ AF: 0.502

Gnomad EAS AF: 0.560

Gnomad SAS AF: 0.637

Gnomad FIN AF: 0.552

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.540

Gnomad OTH AF: 0.505

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

GnomAD4 genome AF: 0.534 AC: 81108 AN: 152018 Hom.: 21713 Cov.: 32 AF XY: 0.533 AC XY: 39583 AN XY: 74292

African (AFR) AF: 0.543 AC: 22495 AN: 41458

American (AMR) AF: 0.434 AC: 6630 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.502 AC: 1743 AN: 3472

East Asian (EAS) AF: 0.559 AC: 2882 AN: 5152

South Asian (SAS) AF: 0.636 AC: 3058 AN: 4808

European-Finnish (FIN) AF: 0.552 AC: 5839 AN: 10582

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.540 AC: 36666 AN: 67956

Other (OTH) AF: 0.508 AC: 1073 AN: 2112

Alfa AF: 0.494 Hom.: 5559

Bravo AF: 0.521

Asia WGS AF: 0.574 AC: 1997 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.65
DANN	Benign	0.26
PhyloP100		-0.64
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: rs1883661; hg19: chr1-15009820; COSMIC: COSV65716616;