Variant chr17-40819075-TGGCCGCCGCCGG-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM4BP6

The NM_000421.5(KRT10):c.1448_1459del(p.Ser483_His487delinsTyr) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000783 in 1,215,240 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0026 ( 0 hom., cov: 24)

Exomes 𝑓: 0.00061 ( 0 hom. )

Consequence

KRT10
NM_000421.5 inframe_deletion

Scores

Not classified

Clinical Significance

Likely benign no assertion criteria provided B: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 Uncertain_significance. Variant got 1 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_000421.5.

BP6

Variant 17-40819075-TGGCCGCCGCCGG-T is Benign according to our data. Variant chr17-40819075-TGGCCGCCGCCGG-T is described in ClinVar as [Likely_benign]. Clinvar id is 3049296.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr17-40819075-TGGCCGCCGCCGG-T is described in Lovd as [Likely_benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRT10	NM_000421.5 linkuse as main transcript	c.1448_1459del	p.Ser483_His487delinsTyr	inframe_deletion	7/8	ENST00000269576.6	NP_000412.4
KRT10	NM_001379366.1 linkuse as main transcript	c.1448_1459del	p.Ser483_His487delinsTyr	inframe_deletion	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.1448_1459del	p.Ser483_His487delinsTyr	inframe_deletion	7/8	1	NM_000421.5	ENSP00000269576	P2
KRT10-AS1	ENST00000301665.9 linkuse as main transcript			upstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.00258

AC:

275

AN:

106732

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00644

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00135

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00205

Gnomad SAS

AF:

0.00478

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000550

Gnomad OTH

AF:

0.00562

GnomAD3 exomes

AF:

0.000955

AC:

AN:

61774

Hom.:

AF XY:

0.000962

AC XY:

AN XY:

36374

show subpopulations

Gnomad AFR exome

AF:

0.00706

Gnomad AMR exome

AF:

0.000524

Gnomad ASJ exome

AF:

0.000194

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00247

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000588

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000609

AC:

675

AN:

1108432

Hom.:

AF XY:

0.000627

AC XY:

343

AN XY:

546724

show subpopulations

Gnomad4 AFR exome

AF:

0.00653

Gnomad4 AMR exome

AF:

0.000770

Gnomad4 ASJ exome

AF:

0.000106

Gnomad4 EAS exome

AF:

0.000686

Gnomad4 SAS exome

AF:

0.00250

Gnomad4 FIN exome

AF:

0.000109

Gnomad4 NFE exome

AF:

0.000286

Gnomad4 OTH exome

AF:

0.00135

GnomAD4 genome

AF:

0.00258

AC:

276

AN:

106808

Hom.:

Cov.:

AF XY:

0.00267

AC XY:

139

AN XY:

52106

show subpopulations

Gnomad4 AFR

AF:

0.00645

Gnomad4 AMR

AF:

0.00135

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00206

Gnomad4 SAS

AF:

0.00481

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000550

Gnomad4 OTH

AF:

0.00554

Alfa

AF:

0.0000843

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

KRT10-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 01, 2024

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

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