Variant 17-40818881-T-TGCTGCCGCCGCCGGA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 2P and 12B. PM4BP6_Very_StrongBS2

The NM_000421.5(KRT10):c.1639_1653dupTCCGGCGGCGGCAGC(p.Ser551_Ser552insSerGlyGlyGlySer) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00305 in 1,525,934 control chromosomes in the GnomAD database, including 25 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0033 ( 3 hom., cov: 33)

Exomes 𝑓: 0.0030 ( 22 hom. )

Consequence

KRT10
NM_000421.5 conservative_inframe_insertion

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.15

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 Benign. Variant got -10 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_000421.5.

BP6

Variant 17-40818881-T-TGCTGCCGCCGCCGGA is Benign according to our data. Variant chr17-40818881-T-TGCTGCCGCCGCCGGA is described in ClinVar as [Likely_benign]. Clinvar id is 808260.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 3 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRT10	NM_000421.5 link	c.1639_1653dupTCCGGCGGCGGCAGC	p.Ser551_Ser552insSerGlyGlyGlySer	conservative_inframe_insertion	7/8	ENST00000269576.6	NP_000412.4	P13645
KRT10	NM_001379366.1 link	c.1639_1653dupTCCGGCGGCGGCAGC	p.Ser551_Ser552insSerGlyGlyGlySer	conservative_inframe_insertion	7/8		NP_001366295.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRT10	ENST00000269576.6 link	c.1639_1653dupTCCGGCGGCGGCAGC	p.Ser551_Ser552insSerGlyGlyGlySer	conservative_inframe_insertion	7/8	1	NM_000421.5	ENSP00000269576.5		P13645
KRT10	ENST00000635956.2 link	c.1639_1653dupTCCGGCGGCGGCAGC	p.Ser551_Ser552insSerGlyGlyGlySer	conservative_inframe_insertion	7/8	2		ENSP00000490524.2		A0A1B0GVI3

Frequencies

GnomAD3 genomes

AF:

0.00327

AC:

486

AN:

148630

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000372

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000935

Gnomad ASJ

AF:

0.00878

Gnomad EAS

AF:

0.000393

Gnomad SAS

AF:

0.00107

Gnomad FIN

AF:

0.0114

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00443

Gnomad OTH

AF:

0.00441

GnomAD3 exomes

AF:

0.00180

AC:

321

AN:

178706

Hom.:

AF XY:

0.00163

AC XY:

166

AN XY:

101592

show subpopulations

Gnomad AFR exome

AF:

0.000267

Gnomad AMR exome

AF:

0.000569

Gnomad ASJ exome

AF:

0.00451

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000202

Gnomad FIN exome

AF:

0.00604

Gnomad NFE exome

AF:

0.00219

Gnomad OTH exome

AF:

0.00237

GnomAD4 exome

AF:

0.00303

AC:

4172

AN:

1377196

Hom.:

Cov.:

AF XY:

0.00296

AC XY:

2028

AN XY:

685136

show subpopulations

Gnomad4 AFR exome

AF:

0.000242

Gnomad4 AMR exome

AF:

0.000825

Gnomad4 ASJ exome

AF:

0.00682

Gnomad4 EAS exome

AF:

0.0000290

Gnomad4 SAS exome

AF:

0.000281

Gnomad4 FIN exome

AF:

0.0108

Gnomad4 NFE exome

AF:

0.00314

Gnomad4 OTH exome

AF:

0.00282

GnomAD4 genome

AF:

0.00327

AC:

486

AN:

148738

Hom.:

Cov.:

AF XY:

0.00355

AC XY:

258

AN XY:

72700

show subpopulations

Gnomad4 AFR

AF:

0.000371

Gnomad4 AMR

AF:

0.000934

Gnomad4 ASJ

AF:

0.00878

Gnomad4 EAS

AF:

0.000394

Gnomad4 SAS

AF:

0.00107

Gnomad4 FIN

AF:

0.0114

Gnomad4 NFE

AF:

0.00443

Gnomad4 OTH

AF:

0.00437

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 07, 2023	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Sep 01, 2024	KRT10: BS2 -

KRT10-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 06, 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