17-40819077-G-GAGCTTCCGCCGCCGGAGCTT

Variant names:

• chr17-40819077-G-GAGCTTCCGCCGCCGGAGCTT
• rs762667965
• NM_000421.5:c.1457_1458insAAGCTCCGGCGGCGGAAGCT

Variant summary

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

The NM_000421.5(KRT10):​c.1457_1458insAAGCTCCGGCGGCGGAAGCT​(p.His487SerfsTer139) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000678 in 145,958 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00068 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000051 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: KRT10 NM_000421.5 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.66

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRT10	NM_000421.5	c.1457_1458insAAGCTCCGGCGGCGGAAGCT	p.His487SerfsTer139	frameshift_variant	Exon 7 of 8	ENST00000269576.6	NP_000412.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRT10	ENST00000269576.6	c.1457_1458insAAGCTCCGGCGGCGGAAGCT	p.His487SerfsTer139	frameshift_variant	Exon 7 of 8	1	NM_000421.5	ENSP00000269576.5

Frequencies

GnomAD3 genomes AF: 0.000686 AC: 100 AN: 145860 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00240

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000203

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000151

Gnomad OTH AF: 0.00101

GnomAD3 exomes AF: 0.0000705 AC: 5 AN: 70924 Hom.: 0 AF XY: 0.0000721 AC XY: 3 AN XY: 41622

Gnomad AFR exome AF: 0.00217

Gnomad AMR exome AF: 0.0000919

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000688

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000497

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000509 AC: 64 AN: 1258140 Hom.: 1 Cov.: 34 AF XY: 0.0000581 AC XY: 36 AN XY: 619688

Gnomad4 AFR exome AF: 0.00206

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000449

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000397

Gnomad4 OTH exome AF: 0.0000968

GnomAD4 genome AF: 0.000678 AC: 99 AN: 145958 Hom.: 0 Cov.: 31 AF XY: 0.000702 AC XY: 50 AN XY: 71222

Gnomad4 AFR AF: 0.00237

Gnomad4 AMR AF: 0.000202

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000152

Gnomad4 OTH AF: 0.00100

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: rs762667965; hg19: chr17-38975329;