17-40819625-CG-TC

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PS1_ModeratePM2PP5

The NM_000421.5(KRT10):​c.1264_1265delinsGA​(p.Arg422Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely pathogenicin UniProt.

Frequency

Genomes: not found (cov: 32)

Consequence

KRT10
NM_000421.5 missense

Scores

Not classified

Clinical Significance

Pathogenic no assertion criteria provided P:1O:1

Conservation

PhyloP100: 4.75
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 5 ACMG points.

PS1
Transcript NM_000421.5 (KRT10) is affected with MISSENSE_VARIANT having same AA change as one Pathogenic present in UniProt
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 17-40819625-CG-TC is Pathogenic according to our data. Variant chr17-40819625-CG-TC is described in ClinVar as [Pathogenic]. Clinvar id is 14580.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
KRT10NM_000421.5 linkuse as main transcriptc.1264_1265delinsGA p.Arg422Glu missense_variant 6/8 ENST00000269576.6
KRT10-AS1NR_160888.1 linkuse as main transcriptn.64+417_64+418delinsTC intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
KRT10ENST00000269576.6 linkuse as main transcriptc.1264_1265delinsGA p.Arg422Glu missense_variant 6/81 NM_000421.5 P2
KRT10-AS1ENST00000301665.9 linkuse as main transcriptn.108+417_108+418delinsTC intron_variant, non_coding_transcript_variant 2

Frequencies

GnomAD3 genomes
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1Other:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Annular epidermolytic ichthyosis Pathogenic:1
Pathogenic, no assertion criteria providedliterature onlyOMIMMar 01, 1997- -
not provided Other:1
not provided, no classification providedliterature onlyEpithelial Biology; Institute of Medical Biology, Singapore-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs59075499; hg19: chr17-38975877; API