chr17-40819076-GGCCGCCGCCGGAGCTT-AG

Variant names:

• chr17-40819076-GGCCGCCGCCGGAGCTT-AG
• rs1555548541
• NM_000421.5:c.1443_1459delAAGCTCCGGCGGCGGCCinsCT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM4 BP6_Moderate

The NM_000421.5(KRT10):​c.1443_1459delAAGCTCCGGCGGCGGCCinsCT​(p.Ser482_His487delinsTyr) variant causes a missense, disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. G481G) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 24)
• Consequence: KRT10 NM_000421.5 missense, disruptive_inframe_deletion
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.66
• Publications: 0 publications found

Genes affected

KRT10 (HGNC:6413): (keratin 10) This gene encodes a member of the type I (acidic) cytokeratin family, which belongs to the superfamily of intermediate filament (IF) proteins. Keratins are heteropolymeric structural proteins which form the intermediate filament. These filaments, along with actin microfilaments and microtubules, compose the cytoskeleton of epithelial cells. Mutations in this gene are associated with epidermolytic hyperkeratosis. This gene is located within a cluster of keratin family members on chromosome 17q21. [provided by RefSeq, Jul 2008]

KRT10-AS1 (HGNC:28305): (KRT10 antisense RNA 1) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_000421.5.
• BP6: Variant 17-40819076-GGCCGCCGCCGGAGCTT-AG is Benign according to our data. Variant chr17-40819076-GGCCGCCGCCGGAGCTT-AG is described in ClinVar as Likely_benign. ClinVar VariationId is 510707.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000421.5. 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
	KRT10	NM_000421.5	MANE Select	c.1443_1459delAAGCTCCGGCGGCGGCCinsCT	p.Ser482_His487delinsTyr	missense disruptive_inframe_deletion	N/A	NP_000412.4
	KRT10	NM_001379366.1		c.1443_1459delAAGCTCCGGCGGCGGCCinsCT	p.Ser482_His487delinsTyr	missense disruptive_inframe_deletion	N/A	NP_001366295.1	A0A1B0GVI3
	KRT10-AS1	NR_160886.1		n.-109_-93delGGCCGCCGCCGGAGCTTinsAG		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRT10	ENST00000269576.6	TSL:1 MANE Select	c.1443_1459delAAGCTCCGGCGGCGGCCinsCT	p.Ser482_His487delinsTyr	missense disruptive_inframe_deletion	N/A	ENSP00000269576.5	P13645
	KRT10	ENST00000635956.2	TSL:2	c.1443_1459delAAGCTCCGGCGGCGGCCinsCT	p.Ser482_His487delinsTyr	missense disruptive_inframe_deletion	N/A	ENSP00000490524.2	A0A1B0GVI3
	KRT10-AS1	ENST00000436612.7	TSL:2	n.6_22delGGCCGCCGCCGGAGCTTinsAG		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes Cov.: 24

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

GnomAD4 genome Cov.: 24

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.7

Splicing

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

Other links and lift over

dbSNP: rs1555548541; hg19: chr17-38975328;