GeneBe

chr17-40819075-T-TA

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000421.5(KRT10):​c.1459_1460insT​(p.His487LeufsTer94) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000375 in 106,738 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: 0.000026 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

KRT10
NM_000421.5 frameshift

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.352
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KRT10NM_000421.5 linkc.1459_1460insT p.His487LeufsTer94 frameshift_variant Exon 7 of 8 ENST00000269576.6 NP_000412.4 P13645

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
KRT10ENST00000269576.6 linkc.1459_1460insT p.His487LeufsTer94 frameshift_variant Exon 7 of 8 1 NM_000421.5 ENSP00000269576.5 P13645

Frequencies

GnomAD3 genomes
AF:
0.0000375
AC:
4
AN:
106738
Hom.:
0
Cov.:
24
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.0000847
Gnomad OTH
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.0000262
AC:
29
AN:
1108468
Hom.:
0
Cov.:
109
AF XY:
0.0000238
AC XY:
13
AN XY:
546744
show subpopulations
Gnomad4 AFR exome
AF:
0.000123
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000457
Gnomad4 SAS exome
AF:
0.0000323
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000249
Gnomad4 OTH exome
AF:
0.0000218
GnomAD4 genome
AF:
0.0000375
AC:
4
AN:
106738
Hom.:
0
Cov.:
24
AF XY:
0.0000384
AC XY:
2
AN XY:
52036
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000847
Gnomad4 OTH
AF:
0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

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: rs764791942; hg19: chr17-38975327; API