Variant 17-40818891-GCCGGAGCTGCCGCCC-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM4BP6BS2

The NM_000421.5(KRT10):c.1629_1643del(p.Gly548_Ser552del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.000894 in 1,327,172 control chromosomes in the GnomAD database, including 25 homozygotes. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0016 ( 0 hom., cov: 23)

Exomes 𝑓: 0.00089 ( 25 hom. )

Failed GnomAD Quality Control

Consequence

KRT10
NM_000421.5 inframe_deletion

Scores

Not classified

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 3.93

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_000421.5.

BP6

Variant 17-40818891-GCCGGAGCTGCCGCCC-G is Benign according to our data. Variant chr17-40818891-GCCGGAGCTGCCGCCC-G is described in ClinVar as [Benign]. Clinvar id is 3053465.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAdExome4 at 25 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRT10	NM_000421.5 linkuse as main transcript	c.1629_1643del	p.Gly548_Ser552del	inframe_deletion	7/8	ENST00000269576.6	NP_000412.4
KRT10	NM_001379366.1 linkuse as main transcript	c.1629_1643del	p.Gly548_Ser552del	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.1629_1643del	p.Gly548_Ser552del	inframe_deletion	7/8	1	NM_000421.5	ENSP00000269576	P2
KRT10	ENST00000635956.2 linkuse as main transcript	c.1629_1643del	p.Gly548_Ser552del	inframe_deletion	7/8	2		ENSP00000490524	A2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

235

AN:

150290

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00203

Gnomad AMI

AF:

0.00442

Gnomad AMR

AF:

0.00139

Gnomad ASJ

AF:

0.000872

Gnomad EAS

AF:

0.00292

Gnomad SAS

AF:

0.00315

Gnomad FIN

AF:

0.00145

Gnomad MID

AF:

0.00321

Gnomad NFE

AF:

0.00111

Gnomad OTH

AF:

0.00146

GnomAD4 exome

AF:

0.000894

AC:

1186

AN:

1327172

Hom.:

AF XY:

0.00106

AC XY:

698

AN XY:

657428

show subpopulations

Gnomad4 AFR exome

AF:

0.00320

Gnomad4 AMR exome

AF:

0.00384

Gnomad4 ASJ exome

AF:

0.00267

Gnomad4 EAS exome

AF:

0.00176

Gnomad4 SAS exome

AF:

0.00363

Gnomad4 FIN exome

AF:

0.00159

Gnomad4 NFE exome

AF:

0.000451

Gnomad4 OTH exome

AF:

0.00102

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00156

AC:

235

AN:

150400

Hom.:

Cov.:

AF XY:

0.00164

AC XY:

121

AN XY:

73576

show subpopulations

Gnomad4 AFR

AF:

0.00203

Gnomad4 AMR

AF:

0.00139

Gnomad4 ASJ

AF:

0.000872

Gnomad4 EAS

AF:

0.00293

Gnomad4 SAS

AF:

0.00315

Gnomad4 FIN

AF:

0.00145

Gnomad4 NFE

AF:

0.00111

Gnomad4 OTH

AF:

0.00144

Alfa

AF:

0.0108

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

KRT10-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 29, 2019

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). -

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