chr12-52473219-CTTG-C

Position:

• chr12-52473219-CTTG-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM4_Supporting PP5_Moderate

The NM_173086.5(KRT6C):​c.516_518delCAA​(p.Asn172del) variant causes a disruptive inframe deletion change. Variant has been reported in ClinVar as Pathogenic (★).

• Frequency: Genomes: not found (cov: 20)
• Consequence: KRT6C NM_173086.5 disruptive_inframe_deletion
• Clinical Significance: Pathogenic criteria provided, single submitter P:2 O:1
• Conservation: PhyloP100: 5.49

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 Uncertain_significance. Variant got 3 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_173086.5. Strenght limited to Supporting due to length of the change: 1aa.
• PP5: Variant 12-52473219-CTTG-C is Pathogenic according to our data. Variant chr12-52473219-CTTG-C is described in ClinVar as [Pathogenic]. Clinvar id is 126525.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr12-52473219-CTTG-C is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRT6C	NM_173086.5	c.516_518delCAA	p.Asn172del	disruptive_inframe_deletion	1/9	ENST00000252250.7	NP_775109.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRT6C	ENST00000252250.7	c.516_518delCAA	p.Asn172del	disruptive_inframe_deletion	1/9	1	NM_173086.5	ENSP00000252250.6

Frequencies

GnomAD3 genomes Cov.: 20

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

GnomAD4 genome Cov.: 20

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:2 Other:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Pathogenic:1 Other:1

Pathogenic, criteria provided, single submitter	clinical testing	Clinical Genetics Laboratory, Skane University Hospital Lund	Dec 27, 2022	- -
not provided, no classification provided	literature only	Epithelial Biology; Institute of Medical Biology, Singapore	-	- -

Focal palmoplantar keratoderma Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Feb 01, 2010

- -

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs267607474; hg19: chr12-52867003;