chr17-40819077-G-GCCGCCGCCGGAGCTTCCGCCGCCGGAGCTT

Variant names:

• chr17-40819077-G-GCCGCCGCCGGAGCTTCCGCCGCCGGAGCTT
• rs753095095
• NM_000421.5:c.1428_1457dupAAGCTCCGGCGGCGGAAGCTCCGGCGGCGG

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.1428_1457dupAAGCTCCGGCGGCGGAAGCTCCGGCGGCGG​(p.Gly486_His487insSerSerGlyGlyGlySerSerGlyGlyGly) variant causes a disruptive inframe insertion 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 INS_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 (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: KRT10 NM_000421.5 disruptive_inframe_insertion
• 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 17-40819077-G-GCCGCCGCCGGAGCTTCCGCCGCCGGAGCTT is Benign according to our data. Variant chr17-40819077-G-GCCGCCGCCGGAGCTTCCGCCGCCGGAGCTT is described in ClinVar as Likely_benign. ClinVar VariationId is 509767.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.1428_1457dupAAGCTCCGGCGGCGGAAGCTCCGGCGGCGG	p.Gly486_His487insSerSerGlyGlyGlySerSerGlyGlyGly	disruptive_inframe_insertion	Exon 7 of 8	NP_000412.4
	KRT10	NM_001379366.1		c.1428_1457dupAAGCTCCGGCGGCGGAAGCTCCGGCGGCGG	p.Gly486_His487insSerSerGlyGlyGlySerSerGlyGlyGly	disruptive_inframe_insertion	Exon 7 of 8	NP_001366295.1	A0A1B0GVI3
	KRT10-AS1	NR_160886.1		n.-108_-107insCCGCCGCCGGAGCTTCCGCCGCCGGAGCTT		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.1428_1457dupAAGCTCCGGCGGCGGAAGCTCCGGCGGCGG	p.Gly486_His487insSerSerGlyGlyGlySerSerGlyGlyGly	disruptive_inframe_insertion	Exon 7 of 8	ENSP00000269576.5	P13645
	KRT10	ENST00000635956.2	TSL:2	c.1428_1457dupAAGCTCCGGCGGCGGAAGCTCCGGCGGCGG	p.Gly486_His487insSerSerGlyGlyGlySerSerGlyGlyGly	disruptive_inframe_insertion	Exon 7 of 8	ENSP00000490524.2	A0A1B0GVI3
	KRT10-AS1	ENST00000301665.10	TSL:2	n.-11_19dupGAGCTTCCGCCGCCGGAGCTTCCGCCGCCG		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 31

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
Mutation Taster		=86/14	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs753095095; hg19: chr17-38975329;