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

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PM4_Supporting

The NM_000421.5(KRT10):c.1683_1684insAGC(p.Ser563dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000619 in 1,406,058 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.00031 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000037 ( 0 hom. )

Consequence

KRT10
NM_000421.5 inframe_insertion

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:3

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:

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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. Strenght limited to Supporting due to length of the change: 1aa.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRT10	NM_000421.5 linkuse as main transcript	c.1683_1684insAGC	p.Ser563dup	inframe_insertion	7/8	ENST00000269576.6	NP_000412.4
KRT10	NM_001379366.1 linkuse as main transcript	c.1683_1684insAGC	p.Ser563dup	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_1684insAGC	p.Ser563dup	inframe_insertion	7/8	1	NM_000421.5	ENSP00000269576	P2
KRT10	ENST00000635956.2 linkuse as main transcript	c.1683_1684insAGC	p.Ser563dup	inframe_insertion	7/8	2		ENSP00000490524	A2

Frequencies

GnomAD3 genomes

AF:

0.000306

AC:

AN:

130756

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00108

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000145

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000246

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000325

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000369

AC:

AN:

1275200

Hom.:

Cov.:

AF XY:

0.0000300

AC XY:

AN XY:

634360

show subpopulations

Gnomad4 AFR exome

AF:

0.00103

Gnomad4 AMR exome

AF:

0.0000257

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000181

Gnomad4 OTH exome

AF:

0.0000383

GnomAD4 genome

AF:

0.000306

AC:

AN:

130858

Hom.:

Cov.:

AF XY:

0.000314

AC XY:

AN XY:

63688

show subpopulations

Gnomad4 AFR

AF:

0.00108

Gnomad4 AMR

AF:

0.000144

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000247

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000325

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000195

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Uncertain:3

Uncertain significance, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 13, 2023	This variant, c.1681_1683dup, results in the insertion of 1 amino acid(s) of the KRT10 protein (p.Ser563dup), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with KRT10-related conditions. ClinVar contains an entry for this variant (Variation ID: 1319423). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -
Uncertain significance, criteria provided, single submitter	clinical testing	GeneDx	Mar 11, 2024	Has not been previously published as pathogenic or benign to our knowledge; In-frame deletion of 1 amino acid in a non-repeat region; Not observed at significant frequency in large population cohorts (gnomAD) -
Uncertain significance, criteria provided, single submitter	clinical testing	Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden	Nov 03, 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