chr17-40818878-A-AGCT
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 1P and 12B. PM4_SupportingBP6_Very_StrongBS2
The NM_000421.5(KRT10):c.1656_1657insAGC(p.Ser553dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000504 in 1,530,434 control chromosomes in the GnomAD database, including 3 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0028 ( 2 hom., cov: 33)
Exomes 𝑓: 0.00026 ( 1 hom. )
Consequence
KRT10
NM_000421.5 inframe_insertion
NM_000421.5 inframe_insertion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -2.05
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -11 ACMG points.
PM4
?
Nonframeshift variant in NON repetitive region in NM_000421.5. Strenght limited to Supporting due to length of the change: 1aa.
BP6
?
Variant 17-40818878-A-AGCT is Benign according to our data. Variant chr17-40818878-A-AGCT is described in ClinVar as [Likely_benign]. Clinvar id is 1541400.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
?
High Homozygotes in GnomAd at 2 AD,AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KRT10 | NM_000421.5 | c.1656_1657insAGC | p.Ser553dup | inframe_insertion | 7/8 | ENST00000269576.6 | |
KRT10 | NM_001379366.1 | c.1656_1657insAGC | p.Ser553dup | inframe_insertion | 7/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KRT10 | ENST00000269576.6 | c.1656_1657insAGC | p.Ser553dup | inframe_insertion | 7/8 | 1 | NM_000421.5 | P2 | |
KRT10 | ENST00000635956.2 | c.1656_1657insAGC | p.Ser553dup | inframe_insertion | 7/8 | 2 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.00278 AC: 412AN: 148342Hom.: 2 Cov.: 33
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GnomAD3 exomes AF: 0.000465 AC: 86AN: 185072Hom.: 1 AF XY: 0.000333 AC XY: 35AN XY: 105042
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GnomAD4 exome AF: 0.000261 AC: 361AN: 1381986Hom.: 1 Cov.: 31 AF XY: 0.000206 AC XY: 142AN XY: 687732
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GnomAD4 genome ? AF: 0.00277 AC: 411AN: 148448Hom.: 2 Cov.: 33 AF XY: 0.00280 AC XY: 203AN XY: 72528
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
KRT10-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Oct 10, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Nov 24, 2023 | - - |
Computational scores
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Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at