rs267607475

Positions:

• chr12-52469683-CCTCCAGCAGCTTGCGGTAGGTGGCGAT-C

Variant summary

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

The NM_173086.5(KRT6C):​c.1384_1410del​(p.Ile462_Glu470del) variant causes a inframe deletion 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: KRT6C NM_173086.5 inframe_deletion
• Clinical Significance: Pathogenic no assertion criteria provided P:1 O:1
• Conservation: PhyloP100: 8.87

Genes affected

KRT6C (HGNC:20406): (keratin 6C) Keratins are intermediate filament proteins responsible for the structural integrity of epithelial cells and are subdivided into epithelial keratins and hair keratins. The type II keratins are clustered in a region of chromosome 12q13. [provided by RefSeq, Jul 2009]

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_173086.5.
• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP
• PP5: Variant 12-52469683-CCTCCAGCAGCTTGCGGTAGGTGGCGAT-C is Pathogenic according to our data. Variant chr12-52469683-CCTCCAGCAGCTTGCGGTAGGTGGCGAT-C is described in ClinVar as [Pathogenic]. Clinvar id is 66966.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr12-52469683-CCTCCAGCAGCTTGCGGTAGGTGGCGAT-C is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRT6C	NM_173086.5	c.1384_1410del	p.Ile462_Glu470del	inframe_deletion	7/9	ENST00000252250.7	NP_775109.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRT6C	ENST00000252250.7	c.1384_1410del	p.Ile462_Glu470del	inframe_deletion	7/9	1	NM_173086.5	ENSP00000252250	P1

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 Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Focal palmoplantar keratoderma Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Feb 01, 2010

- -

not provided Other:1

not provided, no classification provided

literature only

Epithelial Biology; Institute of Medical Biology, Singapore

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- -

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: rs267607475; hg19: chr12-52863467;