chr17-41610341-CGCCCTCCAGCAGGCGGCGGTAGGTGG-GCC

Position:

• chr17-41610341-CGCCCTCCAGCAGGCGGCGGTAGGTGG-GCC

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PM4 PP3 PP5

The NM_005557.4(KRT16):​c.1244_1270delinsGGC​(p.Ala415_Glu424delinsGlyGln) variant causes a protein altering change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: KRT16 NM_005557.4 protein_altering
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 9.26

Genes affected

KRT16 (HGNC:6423): (keratin 16) The protein encoded by this gene is a member of the keratin gene family. The keratins are intermediate filament proteins responsible for the structural integrity of epithelial cells and are subdivided into cytokeratins and hair keratins. Most of the type I cytokeratins consist of acidic proteins which are arranged in pairs of heterotypic keratin chains and are clustered in a region of chromosome 17q12-q21. This keratin has been coexpressed with keratin 14 in a number of epithelial tissues, including esophagus, tongue, and hair follicles. Mutations in this gene are associated with type 1 pachyonychia congenita, non-epidermolytic palmoplantar keratoderma and unilateral palmoplantar verrucous nevus. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_005557.4.
• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP
• PP5: Variant 17-41610341-CGCCCTCCAGCAGGCGGCGGTAGGTGG-GCC is Pathogenic according to our data. Variant chr17-41610341-CGCCCTCCAGCAGGCGGCGGTAGGTGG-GCC is described in ClinVar as [Pathogenic]. Clinvar id is 14610.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRT16	NM_005557.4	c.1244_1270delinsGGC	p.Ala415_Glu424delinsGlyGln	protein_altering_variant	6/8	ENST00000301653.9	NP_005548.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRT16	ENST00000301653.9	c.1244_1270delinsGGC	p.Ala415_Glu424delinsGlyGln	protein_altering_variant	6/8	1	NM_005557.4	ENSP00000301653	P1
KRT16	ENST00000593067.1			downstream_gene_variant		3		ENSP00000467124

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Palmoplantar keratoderma, nonepidermolytic, focal 1 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jun 01, 2000

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1555573633; hg19: chr17-39766593;