chr1-15044151-C-G

Variant names:

• chr1-15044151-C-G
• rs1673219810
• NM_201628.3:c.718C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_201628.3(KAZN):​c.718C>G​(p.Leu240Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 30)
• Consequence: KAZN NM_201628.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.90
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.718C>G	p.Leu240Val	missense	Exon 4 of 15	NP_963922.2	Q674X7-1
	KAZN	NM_001437721.1		c.718C>G	p.Leu240Val	missense	Exon 5 of 9	NP_001424650.1
	KAZN	NM_015209.3		c.718C>G	p.Leu240Val	missense	Exon 4 of 8	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.718C>G	p.Leu240Val	missense	Exon 4 of 15	ENSP00000365198.2	Q674X7-1
	KAZN	ENST00000503743.5	TSL:1	c.718C>G	p.Leu240Val	missense	Exon 5 of 9	ENSP00000426015.1	Q674X7-2
	KAZN	ENST00000361144.9	TSL:1	c.700C>G	p.Leu234Val	missense	Exon 4 of 8	ENSP00000354727.5	Q674X7-3

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.53
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.030
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.039	T
Eigen	Uncertain	0.66
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.083	D
MetaRNN	Uncertain	0.51	D
MetaSVM	Uncertain	-0.18	T
MutationAssessor	Benign	0.90	L
PhyloP100		3.9
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.28
Sift	Benign	0.10	T
Sift4G	Uncertain	0.018	D
Polyphen		1.0	D
Vest4		0.81
MutPred		0.24		Gain of methylation at K244 (P = 0.0924)
MVP		0.73
MPC		1.7
ClinPred		0.90	D
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.34
gMVP		0.95
Mutation Taster		=46/54	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1673219810; hg19: chr1-15370647;