17-40818880-C-CGCTGCCGCCGCCGTATCCGCCGCCGGAGCT

Position:

• chr17-40818880-C-CGCTGCCGCCGCCGTATCCGCCGCCGGAGCT

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM2 PM4 BP6_Moderate

The NM_000421.5(KRT10):​c.1654_1655insAGCTCCGGCGGCGGATACGGCGGCGGCAGC​(p.Ser552delinsLysLeuArgArgArgIleArgArgArgGlnArg) variant causes a protein altering change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: KRT10 NM_000421.5 protein_altering
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.535

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_000421.5.
• BP6: Variant 17-40818880-C-CGCTGCCGCCGCCGTATCCGCCGCCGGAGCT is Benign according to our data. Variant chr17-40818880-C-CGCTGCCGCCGCCGTATCCGCCGCCGGAGCT is described in ClinVar as [Benign]. Clinvar id is 1291201.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KRT10	NM_000421.5	c.1654_1655insAGCTCCGGCGGCGGATACGGCGGCGGCAGC	p.Ser552delinsLysLeuArgArgArgIleArgArgArgGlnArg	protein_altering_variant	7/8	ENST00000269576.6
KRT10	NM_001379366.1	c.1654_1655insAGCTCCGGCGGCGGATACGGCGGCGGCAGC	p.Ser552delinsLysLeuArgArgArgIleArgArgArgGlnArg	protein_altering_variant	7/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KRT10	ENST00000269576.6	c.1654_1655insAGCTCCGGCGGCGGATACGGCGGCGGCAGC	p.Ser552delinsLysLeuArgArgArgIleArgArgArgGlnArg	protein_altering_variant	7/8	1	NM_000421.5	P2
KRT10	ENST00000635956.2	c.1654_1655insAGCTCCGGCGGCGGATACGGCGGCGGCAGC	p.Ser552delinsLysLeuArgArgArgIleArgArgArgGlnArg	protein_altering_variant	7/8	2		A2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-38975132;