dbSNP rs762667965: KRT10:p.His487SerfsTer134 (chr17-40819077-G-GAGCTT) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_000421.5(KRT10):c.1457_1458insAAGCT(p.His487SerfsTer134) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0219 in 145,920 control chromosomes in the GnomAD database, including 131 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.022 ( 131 hom., cov: 31)

Exomes 𝑓: 0.0029 ( 82 hom. )

Failed GnomAD Quality Control

Consequence

KRT10
NM_000421.5 frameshift

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter U:2B:1

Conservation

PhyloP100: 2.66

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 -10 ACMG points.

BP6

Variant 17-40819077-G-GAGCTT is Benign according to our data. Variant chr17-40819077-G-GAGCTT is described in ClinVar as [Benign]. Clinvar id is 1175680.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0729 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRT10	NM_000421.5 link	c.1457_1458insAAGCT	p.His487SerfsTer134	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.1457_1458insAAGCT	p.His487SerfsTer134	frameshift_variant	Exon 7 of 8	1	NM_000421.5	ENSP00000269576.5		P13645

Frequencies

GnomAD3 genomes

AF:

0.0219

AC:

3188

AN:

145822

Hom.:

132

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0752

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00682

Gnomad ASJ

AF:

0.00561

Gnomad EAS

AF:

0.00389

Gnomad SAS

AF:

0.000665

Gnomad FIN

AF:

0.000604

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000848

Gnomad OTH

AF:

0.0207

GnomAD3 exomes

AF:

0.00235

AC:

167

AN:

70924

Hom.:

AF XY:

0.00214

AC XY:

AN XY:

41622

show subpopulations

Gnomad AFR exome

AF:

0.0674

Gnomad AMR exome

AF:

0.00257

Gnomad ASJ exome

AF:

0.00482

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00124

Gnomad FIN exome

AF:

0.000206

Gnomad NFE exome

AF:

0.000845

Gnomad OTH exome

AF:

0.00199

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00293

AC:

3689

AN:

1257990

Hom.:

Cov.:

AF XY:

0.00269

AC XY:

1667

AN XY:

619622

show subpopulations

Gnomad4 AFR exome

AF:

0.0786

Gnomad4 AMR exome

AF:

0.00389

Gnomad4 ASJ exome

AF:

0.00550

Gnomad4 EAS exome

AF:

0.000965

Gnomad4 SAS exome

AF:

0.000793

Gnomad4 FIN exome

AF:

0.000876

Gnomad4 NFE exome

AF:

0.00107

Gnomad4 OTH exome

AF:

0.00589

GnomAD4 genome

AF:

0.0219

AC:

3196

AN:

145920

Hom.:

131

Cov.:

AF XY:

0.0209

AC XY:

1485

AN XY:

71206

show subpopulations

Gnomad4 AFR

AF:

0.0752

Gnomad4 AMR

AF:

0.00682

Gnomad4 ASJ

AF:

0.00561

Gnomad4 EAS

AF:

0.00349

Gnomad4 SAS

AF:

0.000665

Gnomad4 FIN

AF:

0.000604

Gnomad4 NFE

AF:

0.000848

Gnomad4 OTH

AF:

0.0205

Alfa

AF:

0.000448

Hom.:

ClinVar

Significance: Benign

Submissions summary: Uncertain:2Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:2Benign:1

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

- -

May 04, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

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