Variant 17-40818851-A-AGCTGCCGCCGCCGTATCCGCCGCCGGAGCT details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PM4BP6_Very_StrongBA1

The NM_000421.5(KRT10):c.1683_1684insAGCTCCGGCGGCGGATACGGCGGCGGCAGC(p.Gly556_Gly565dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0897 in 1,344,600 control chromosomes in the GnomAD database, including 10,425 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 2321 hom., cov: 33)

Exomes 𝑓: 0.083 ( 8104 hom. )

Consequence

KRT10
NM_000421.5 inframe_insertion

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.0440

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_000421.5.

BP6

Variant 17-40818851-A-AGCTGCCGCCGCCGTATCCGCCGCCGGAGCT is Benign according to our data. Variant chr17-40818851-A-AGCTGCCGCCGCCGTATCCGCCGCCGGAGCT is described in ClinVar as [Likely_benign]. Clinvar id is 516735.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.293 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRT10	NM_000421.5 linkuse as main transcript	c.1683_1684insAGCTCCGGCGGCGGATACGGCGGCGGCAGC	p.Gly556_Gly565dup	inframe_insertion	7/8	ENST00000269576.6	NP_000412.4
KRT10	NM_001379366.1 linkuse as main transcript	c.1683_1684insAGCTCCGGCGGCGGATACGGCGGCGGCAGC	p.Gly556_Gly565dup	inframe_insertion	7/8		NP_001366295.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRT10	ENST00000269576.6 linkuse as main transcript	c.1683_1684insAGCTCCGGCGGCGGATACGGCGGCGGCAGC	p.Gly556_Gly565dup	inframe_insertion	7/8	1	NM_000421.5	ENSP00000269576	P2
KRT10	ENST00000635956.2 linkuse as main transcript	c.1683_1684insAGCTCCGGCGGCGGATACGGCGGCGGCAGC	p.Gly556_Gly565dup	inframe_insertion	7/8	2		ENSP00000490524	A2

Frequencies

GnomAD3 genomes

AF:

0.157

AC:

20235

AN:

129164

Hom.:

2319

Cov.:

show subpopulations

Gnomad AFR

AF:

0.298

Gnomad AMI

AF:

0.0542

Gnomad AMR

AF:

0.106

Gnomad ASJ

AF:

0.113

Gnomad EAS

AF:

0.188

Gnomad SAS

AF:

0.192

Gnomad FIN

AF:

0.0837

Gnomad MID

AF:

0.146

Gnomad NFE

AF:

0.104

Gnomad OTH

AF:

0.150

GnomAD4 exome

AF:

0.0826

AC:

100365

AN:

1215346

Hom.:

8104

Cov.:

AF XY:

0.0829

AC XY:

50199

AN XY:

605680

show subpopulations

Gnomad4 AFR exome

AF:

0.250

Gnomad4 AMR exome

AF:

0.0428

Gnomad4 ASJ exome

AF:

0.0724

Gnomad4 EAS exome

AF:

0.173

Gnomad4 SAS exome

AF:

0.110

Gnomad4 FIN exome

AF:

0.0817

Gnomad4 NFE exome

AF:

0.0744

Gnomad4 OTH exome

AF:

0.0998

GnomAD4 genome

AF:

0.157

AC:

20246

AN:

129254

Hom.:

2321

Cov.:

AF XY:

0.156

AC XY:

9817

AN XY:

62940

show subpopulations

Gnomad4 AFR

AF:

0.298

Gnomad4 AMR

AF:

0.106

Gnomad4 ASJ

AF:

0.113

Gnomad4 EAS

AF:

0.188

Gnomad4 SAS

AF:

0.192

Gnomad4 FIN

AF:

0.0837

Gnomad4 NFE

AF:

0.104

Gnomad4 OTH

AF:

0.148

Alfa

AF:

0.0296

Hom.:

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 14, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

KRT10-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 05, 2020

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

Epidermolytic ichthyosis;C1843463:Annular epidermolytic ichthyosis;C3665704:Congenital reticular ichthyosiform erythroderma

Benign:1

Benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Aug 11, 2021

- -

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