Variant chr17-40819089-GCTT-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 1P and 1B. PM4_SupportingBP6

The NM_000421.5(KRT10):c.1443_1445delAAG(p.Ser482del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000637 in 1,442,054 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0018 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00050 ( 0 hom. )

Consequence

KRT10
NM_000421.5 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -1.33

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 Uncertain_significance. Variant got 0 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_000421.5. Strenght limited to Supporting due to length of the change: 1aa.

BP6

Variant 17-40819089-GCTT-G is Benign according to our data. Variant chr17-40819089-GCTT-G is described in ClinVar as [Likely_benign]. Clinvar id is 3050459.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRT10	NM_000421.5 link	c.1443_1445delAAG	p.Ser482del	disruptive_inframe_deletion	Exon 7 of 8	ENST00000269576.6	NP_000412.4	P13645
KRT10	NM_001379366.1 link	c.1443_1445delAAG	p.Ser482del	disruptive_inframe_deletion	Exon 7 of 8		NP_001366295.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRT10	ENST00000269576.6 link	c.1443_1445delAAG	p.Ser482del	disruptive_inframe_deletion	Exon 7 of 8	1	NM_000421.5	ENSP00000269576.5		P13645

Frequencies

GnomAD3 genomes

AF:

0.00182

AC:

272

AN:

149648

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00501

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000997

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00118

Gnomad SAS

AF:

0.00299

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000372

Gnomad OTH

AF:

0.00389

GnomAD3 exomes

AF:

0.000612

AC:

AN:

96464

Hom.:

AF XY:

0.000648

AC XY:

AN XY:

55588

show subpopulations

Gnomad AFR exome

AF:

0.00289

Gnomad AMR exome

AF:

0.000317

Gnomad ASJ exome

AF:

0.000140

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00180

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000366

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000499

AC:

645

AN:

1292304

Hom.:

AF XY:

0.000516

AC XY:

329

AN XY:

637804

show subpopulations

Gnomad4 AFR exome

AF:

0.00597

Gnomad4 AMR exome

AF:

0.000523

Gnomad4 ASJ exome

AF:

0.0000872

Gnomad4 EAS exome

AF:

0.000540

Gnomad4 SAS exome

AF:

0.00218

Gnomad4 FIN exome

AF:

0.0000934

Gnomad4 NFE exome

AF:

0.000223

Gnomad4 OTH exome

AF:

0.00112

GnomAD4 genome

AF:

0.00182

AC:

273

AN:

149750

Hom.:

Cov.:

AF XY:

0.00187

AC XY:

137

AN XY:

73130

show subpopulations

Gnomad4 AFR

AF:

0.00502

Gnomad4 AMR

AF:

0.000996

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00118

Gnomad4 SAS

AF:

0.00299

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000372

Gnomad4 OTH

AF:

0.00385

Alfa

AF:

0.000122

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

KRT10-related disorder

Benign:1

Feb 01, 2024

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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

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.

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