GeneBe

NM_000421.5:c.1683_1684insAGCTCCGGCGGCGGATACGGCGGCGGCAGCAGC

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM4

The NM_000421.5(KRT10):​c.1683_1684insAGCTCCGGCGGCGGATACGGCGGCGGCAGCAGC​(p.Ser561_Ser562insSerSerGlyGlyGlyTyrGlyGlyGlySerSer) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000213 in 1,406,290 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000076 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000016 ( 0 hom. )

Consequence

KRT10
NM_000421.5 conservative_inframe_insertion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0440

Publications

0 publications found
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 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.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
KRT10
NM_000421.5
MANE Select
c.1683_1684insAGCTCCGGCGGCGGATACGGCGGCGGCAGCAGCp.Ser561_Ser562insSerSerGlyGlyGlyTyrGlyGlyGlySerSer
conservative_inframe_insertion
Exon 7 of 8NP_000412.4
KRT10
NM_001379366.1
c.1683_1684insAGCTCCGGCGGCGGATACGGCGGCGGCAGCAGCp.Ser561_Ser562insSerSerGlyGlyGlyTyrGlyGlyGlySerSer
conservative_inframe_insertion
Exon 7 of 8NP_001366295.1A0A1B0GVI3

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
KRT10
ENST00000269576.6
TSL:1 MANE Select
c.1683_1684insAGCTCCGGCGGCGGATACGGCGGCGGCAGCAGCp.Ser561_Ser562insSerSerGlyGlyGlyTyrGlyGlyGlySerSer
conservative_inframe_insertion
Exon 7 of 8ENSP00000269576.5P13645
KRT10
ENST00000635956.2
TSL:2
c.1683_1684insAGCTCCGGCGGCGGATACGGCGGCGGCAGCAGCp.Ser561_Ser562insSerSerGlyGlyGlyTyrGlyGlyGlySerSer
conservative_inframe_insertion
Exon 7 of 8ENSP00000490524.2A0A1B0GVI3
KRT10-AS1
ENST00000301665.10
TSL:2
n.-247_-246insGCTGCTGCCGCCGCCGTATCCGCCGCCGGAGCT
upstream_gene
N/A

Frequencies

GnomAD3 genomes
AF:
0.00000765
AC:
1
AN:
130764
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000308
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000157
AC:
2
AN:
1275526
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
634512
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.00
AC:
0
AN:
25136
American (AMR)
AF:
0.00
AC:
0
AN:
38838
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
23198
East Asian (EAS)
AF:
0.00
AC:
0
AN:
33126
South Asian (SAS)
AF:
0.00
AC:
0
AN:
70904
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
33378
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
4916
European-Non Finnish (NFE)
AF:
0.00000201
AC:
2
AN:
993770
Other (OTH)
AF:
0.00
AC:
0
AN:
52260
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00233887), 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
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
AF:
0.00000765
AC:
1
AN:
130764
Hom.:
0
Cov.:
33
AF XY:
0.0000157
AC XY:
1
AN XY:
63586
show subpopulations
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.0000308
AC:
1
AN:
32418
American (AMR)
AF:
0.00
AC:
0
AN:
13838
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3206
East Asian (EAS)
AF:
0.00
AC:
0
AN:
4062
South Asian (SAS)
AF:
0.00
AC:
0
AN:
3966
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
8870
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
272
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
61560
Other (OTH)
AF:
0.00
AC:
0
AN:
1764
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.325
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
PhyloP100
-0.044
Mutation Taster
=85/15
polymorphism

Splicing

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

Publications

Other links and lift over

dbSNP: rs1555548360; hg19: chr17-38975103; API