NM_000421.5:c.1683_1684insAGCGCCGGCGGCGGATACGGCGGCGGCAGCAGCTCCGGCGGCGGATACGGCGGCGGCAGC

Variant names:

• chr17-40818851-A-AGCTGCCGCCGCCGTATCCGCCGCCGGAGCTGCTGCCGCCGCCGTATCCGCCGCCGGCGCT
• rs776920005
• NM_000421.5:c.1683_1684insAGCGCCGGCGGCGGATACGGCGGCGGCAGCAGCTCCGGCGGCGGATACGGCGGCGGCAGC

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PM4

The NM_000421.5(KRT10):​c.1683_1684insAGCGCCGGCGGCGGATACGGCGGCGGCAGCAGCTCCGGCGGCGGATACGGCGGCGGCAGC​(p.Ser561_Ser562insSerAlaGlyGlyGlyTyrGlyGlyGlySerSerSerGlyGlyGlyTyrGlyGlyGlySer) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: KRT10 NM_000421.5 conservative_inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0440

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_000421.5.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRT10	NM_000421.5	c.1683_1684insAGCGCCGGCGGCGGATACGGCGGCGGCAGCAGCTCCGGCGGCGGATACGGCGGCGGCAGC	p.Ser561_Ser562insSerAlaGlyGlyGlyTyrGlyGlyGlySerSerSerGlyGlyGlyTyrGlyGlyGlySer	conservative_inframe_insertion	Exon 7 of 8	ENST00000269576.6	NP_000412.4
KRT10	NM_001379366.1	c.1683_1684insAGCGCCGGCGGCGGATACGGCGGCGGCAGCAGCTCCGGCGGCGGATACGGCGGCGGCAGC	p.Ser561_Ser562insSerAlaGlyGlyGlyTyrGlyGlyGlySerSerSerGlyGlyGlyTyrGlyGlyGlySer	conservative_inframe_insertion	Exon 7 of 8		NP_001366295.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRT10	ENST00000269576.6	c.1683_1684insAGCGCCGGCGGCGGATACGGCGGCGGCAGCAGCTCCGGCGGCGGATACGGCGGCGGCAGC	p.Ser561_Ser562insSerAlaGlyGlyGlyTyrGlyGlyGlySerSerSerGlyGlyGlyTyrGlyGlyGlySer	conservative_inframe_insertion	Exon 7 of 8	1	NM_000421.5	ENSP00000269576.5
KRT10	ENST00000635956.2	c.1683_1684insAGCGCCGGCGGCGGATACGGCGGCGGCAGCAGCTCCGGCGGCGGATACGGCGGCGGCAGC	p.Ser561_Ser562insSerAlaGlyGlyGlyTyrGlyGlyGlySerSerSerGlyGlyGlyTyrGlyGlyGlySer	conservative_inframe_insertion	Exon 7 of 8	2		ENSP00000490524.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs776920005; hg19: chr17-38975103;