17-40819075-T-TTCCGCCGCC
Variant summary
Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM4
The NM_000421.5(KRT10):c.1459_1460insGGCGGCGGA(p.His487delinsArgArgArgAsn) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 1,215,212 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 0.000037 ( 0 hom., cov: 24)
Exomes 𝑓: 0.0000036 ( 0 hom. )
Consequence
KRT10
NM_000421.5 conservative_inframe_insertion
NM_000421.5 conservative_inframe_insertion
Scores
Not classified
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.352
Publications
3 publications found
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 was made for transcript
Our verdict: Uncertain_significance. The variant received 2 ACMG points.
PM4
Nonframeshift variant in NON repetitive region in NM_000421.5.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_000421.5. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| KRT10 | MANE Select | c.1459_1460insGGCGGCGGA | p.His487delinsArgArgArgAsn | conservative_inframe_insertion | Exon 7 of 8 | NP_000412.4 | |||
| KRT10 | c.1459_1460insGGCGGCGGA | p.His487delinsArgArgArgAsn | conservative_inframe_insertion | Exon 7 of 8 | NP_001366295.1 | A0A1B0GVI3 | |||
| KRT10-AS1 | n.-110_-109insTCCGCCGCC | upstream_gene | N/A |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| KRT10 | TSL:1 MANE Select | c.1459_1460insGGCGGCGGA | p.His487delinsArgArgArgAsn | conservative_inframe_insertion | Exon 7 of 8 | ENSP00000269576.5 | P13645 | ||
| KRT10 | TSL:2 | c.1459_1460insGGCGGCGGA | p.His487delinsArgArgArgAsn | conservative_inframe_insertion | Exon 7 of 8 | ENSP00000490524.2 | A0A1B0GVI3 | ||
| KRT10-AS1 | TSL:2 | n.5_6insTCCGCCGCC | non_coding_transcript_exon | Exon 1 of 3 |
Frequencies
GnomAD3 genomes 0.0000375 AC: 4AN: 106738Hom.: 0 Cov.: 24 show subpopulations
GnomAD3 genomes
AF:
AC:
4
AN:
106738
Hom.:
Cov.:
24
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.00000361 AC: 4AN: 1108474Hom.: 0 Cov.: 109 AF XY: 0.00000183 AC XY: 1AN XY: 546748 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
4
AN:
1108474
Hom.:
Cov.:
109
AF XY:
AC XY:
1
AN XY:
546748
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
24368
American (AMR)
AF:
AC:
1
AN:
19474
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
18956
East Asian (EAS)
AF:
AC:
0
AN:
21860
South Asian (SAS)
AF:
AC:
0
AN:
61964
European-Finnish (FIN)
AF:
AC:
0
AN:
27590
Middle Eastern (MID)
AF:
AC:
0
AN:
3498
European-Non Finnish (NFE)
AF:
AC:
2
AN:
884894
Other (OTH)
AF:
AC:
1
AN:
45870
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000148366), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.350
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome 0.0000375 AC: 4AN: 106738Hom.: 0 Cov.: 24 AF XY: 0.0000192 AC XY: 1AN XY: 52036 show subpopulations ⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
GnomAD4 genome
AF:
AC:
4
AN:
106738
Hom.:
Cov.:
24
AF XY:
AC XY:
1
AN XY:
52036
show subpopulations
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
3
AN:
32008
American (AMR)
AF:
AC:
1
AN:
11118
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
2330
East Asian (EAS)
AF:
AC:
0
AN:
2932
South Asian (SAS)
AF:
AC:
0
AN:
2928
European-Finnish (FIN)
AF:
AC:
0
AN:
6072
Middle Eastern (MID)
AF:
AC:
0
AN:
162
European-Non Finnish (NFE)
AF:
AC:
0
AN:
47250
Other (OTH)
AF:
AC:
0
AN:
1424
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000396870), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.363
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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