Genetic Variant KRT10:p.His487ArgfsTer97 (chr17-40819075-T-TAGCCACCGCC) – ACMG Classification: Likely_pathogenic (8 pts)

Variant summary

Our verdict is Likely pathogenic. The variant received 8 ACMG points: 8P and 0B. PVS1

The NM_000421.5(KRT10):c.1459_1460insGGCGGTGGCT(p.His487ArgfsTer97) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000354 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. Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.00030 ( 0 hom., cov: 24)

Exomes 𝑓: 0.0000099 ( 0 hom. )

Consequence

KRT10
NM_000421.5 frameshift

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.352

Publications

3 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 links:

KRT10-AS1 (HGNC:28305): (KRT10 antisense RNA 1) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

KRT10-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_pathogenic. The variant received 8 ACMG points.

PVS1

Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KRT10	NM_000421.5	MANE Select	c.1459_1460insGGCGGTGGCT	p.His487ArgfsTer97	frameshift	Exon 7 of 8	NP_000412.4
KRT10	NM_001379366.1		c.1459_1460insGGCGGTGGCT	p.His487ArgfsTer97	frameshift	Exon 7 of 8	NP_001366295.1	A0A1B0GVI3
KRT10-AS1	NR_160886.1		n.-110_-109insAGCCACCGCC		upstream_gene	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KRT10	ENST00000269576.6	TSL:1 MANE Select	c.1459_1460insGGCGGTGGCT	p.His487ArgfsTer97	frameshift	Exon 7 of 8	ENSP00000269576.5	P13645
KRT10	ENST00000635956.2	TSL:2	c.1459_1460insGGCGGTGGCT	p.His487ArgfsTer97	frameshift	Exon 7 of 8	ENSP00000490524.2	A0A1B0GVI3
KRT10-AS1	ENST00000436612.7	TSL:2	n.5_6insAGCCACCGCC		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes

AF:

0.000300

AC:

AN:

106738

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000625

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000899

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:

0.00140

GnomAD2 exomes

AF:

0.0000162

AC:

AN:

61774

AF XY:

0.0000275

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000105

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000992

AC:

AN:

1108474

Hom.:

Cov.:

109

AF XY:

0.00000549

AC XY:

AN XY:

546748

show subpopulations

African (AFR)

AF:

0.000246

AC:

AN:

24368

American (AMR)

AF:

0.0000514

AC:

AN:

19474

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18956

East Asian (EAS)

AF:

0.00

AC:

AN:

21860

South Asian (SAS)

AF:

0.00

AC:

AN:

61964

European-Finnish (FIN)

AF:

0.00

AC:

AN:

27590

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3498

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

884894

Other (OTH)

AF:

0.0000872

AC:

AN:

45870

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

AF:

0.000300

AC:

AN:

106738

Hom.:

Cov.:

AF XY:

0.000307

AC XY:

AN XY:

52036

show subpopulations

African (AFR)

AF:

0.000625

AC:

AN:

32008

American (AMR)

AF:

0.000899

AC:

AN:

11118

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2330

East Asian (EAS)

AF:

0.00

AC:

AN:

2932

South Asian (SAS)

AF:

0.00

AC:

AN:

2928

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6072

Middle Eastern (MID)

AF:

0.00

AC:

AN:

162

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

47250

Other (OTH)

AF:

0.00140

AC:

AN:

1424

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.35

Mutation Taster

=144/56

polymorphism

(source)

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over