Genetic Variant NM_000421.5:c.1459_1460insGGCGGCGGCT (chr17-40819075-T-TAGCCGCCGCC) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_000421.5(KRT10):c.1459_1460insGGCGGCGGCT(p.His487ArgfsTer97) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0294 in 106,746 control chromosomes in the GnomAD database, including 142 homozygotes. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: 𝑓 0.029 ( 142 hom., cov: 24)

Exomes 𝑓: 0.0032 ( 83 hom. )

Failed GnomAD Quality Control

Consequence

KRT10
NM_000421.5 frameshift

Scores

Not classified

Clinical Significance

Uncertain significance no assertion criteria provided U:2

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 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 made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0885 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRT10	NM_000421.5 link	c.1459_1460insGGCGGCGGCT	p.His487ArgfsTer97	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
KRT10	ENST00000269576.6 link	c.1459_1460insGGCGGCGGCT	p.His487ArgfsTer97	frameshift_variant	Exon 7 of 8	1	NM_000421.5	ENSP00000269576.5		P13645

Frequencies

GnomAD3 genomes

AF:

0.0294

AC:

3131

AN:

106670

Hom.:

143

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0913

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00783

Gnomad ASJ

AF:

0.00815

Gnomad EAS

AF:

0.00580

Gnomad SAS

AF:

0.00102

Gnomad FIN

AF:

0.000165

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000974

Gnomad OTH

AF:

0.0288

GnomAD3 exomes

AF:

0.00217

AC:

134

AN:

61774

Hom.:

AF XY:

0.00190

AC XY:

AN XY:

36374

show subpopulations

Gnomad AFR exome

AF:

0.0624

Gnomad AMR exome

AF:

0.00210

Gnomad ASJ exome

AF:

0.00465

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00108

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000823

Gnomad OTH exome

AF:

0.00118

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00315

AC:

3492

AN:

1108360

Hom.:

Cov.:

109

AF XY:

0.00292

AC XY:

1595

AN XY:

546698

show subpopulations

Gnomad4 AFR exome

AF:

0.0821

Gnomad4 AMR exome

AF:

0.00426

Gnomad4 ASJ exome

AF:

0.00617

Gnomad4 EAS exome

AF:

0.000640

Gnomad4 SAS exome

AF:

0.000807

Gnomad4 FIN exome

AF:

0.000290

Gnomad4 NFE exome

AF:

0.00104

Gnomad4 OTH exome

AF:

0.00643

GnomAD4 genome

AF:

0.0294

AC:

3138

AN:

106746

Hom.:

142

Cov.:

AF XY:

0.0281

AC XY:

1464

AN XY:

52080

show subpopulations

Gnomad4 AFR

AF:

0.0913

Gnomad4 AMR

AF:

0.00782

Gnomad4 ASJ

AF:

0.00815

Gnomad4 EAS

AF:

0.00514

Gnomad4 SAS

AF:

0.00103

Gnomad4 FIN

AF:

0.000165

Gnomad4 NFE

AF:

0.000974

Gnomad4 OTH

AF:

0.0284

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

not provided

Uncertain:2

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over