rs267607474

Variant names:

• chr12-52473219-CTTG-C
• rs267607474
• NM_173086.5:c.516_518delCAA

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 3 publications found

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]

KRT6C Gene-Disease associations (from GenCC):

• palmoplantar keratoderma, nonepidermolytic, focal or diffuse

  Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 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 VariationId is 126525.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173086.5. 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
	KRT6C	NM_173086.5	MANE Select	c.516_518delCAA	p.Asn172del	disruptive_inframe_deletion	Exon 1 of 9	NP_775109.2	P48668

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRT6C	ENST00000252250.7	TSL:1 MANE Select	c.516_518delCAA	p.Asn172del	disruptive_inframe_deletion	Exon 1 of 9	ENSP00000252250.6	P48668

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

ClinVar submissions

Significance: Pathogenic

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
1	-	-	Focal palmoplantar keratoderma (1)
1	-	-	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.5
Mutation Taster		=63/37	disease causing (ClinVar)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs267607474;

hg19: chr12-52867003;

COSMIC: COSV52878679;

COSMIC: COSV52878679;