Genetic Variant NM_000421.5:c.1683_1684insAGCTCCGGCGGCGGATTCGGCGGCGGCAGCAGCTCCGGCGGCGGATACGGCGGCGGCAGC (chr17-40818851-A-AGCTGCCGCCGCCGTATCCGCCGCCGGAGCTGCTGCCGCCGCCGAATCCGCCGCCGGAGCT) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PM4

The NM_000421.5(KRT10):c.1683_1684insAGCTCCGGCGGCGGATTCGGCGGCGGCAGCAGCTCCGGCGGCGGATACGGCGGCGGCAGC(p.Ser561_Ser562insSerSerGlyGlyGlyPheGlyGlyGlySerSerSerGlyGlyGlyTyrGlyGlyGlySer) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000356 in 1,406,392 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000076 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000031 ( 1 hom. )

Consequence

KRT10
NM_000421.5 conservative_inframe_insertion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

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:

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 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PM4

Nonframeshift variant in NON repetitive region in NM_000421.5.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRT10	NM_000421.5 link	c.1683_1684insAGCTCCGGCGGCGGATTCGGCGGCGGCAGCAGCTCCGGCGGCGGATACGGCGGCGGCAGC	p.Ser561_Ser562insSerSerGlyGlyGlyPheGlyGlyGlySerSerSerGlyGlyGlyTyrGlyGlyGlySer	conservative_inframe_insertion	Exon 7 of 8	ENST00000269576.6	NP_000412.4	P13645
KRT10	NM_001379366.1 link	c.1683_1684insAGCTCCGGCGGCGGATTCGGCGGCGGCAGCAGCTCCGGCGGCGGATACGGCGGCGGCAGC	p.Ser561_Ser562insSerSerGlyGlyGlyPheGlyGlyGlySerSerSerGlyGlyGlyTyrGlyGlyGlySer	conservative_inframe_insertion	Exon 7 of 8		NP_001366295.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
KRT10	ENST00000269576.6 link	c.1683_1684insAGCTCCGGCGGCGGATTCGGCGGCGGCAGCAGCTCCGGCGGCGGATACGGCGGCGGCAGC	p.Ser561_Ser562insSerSerGlyGlyGlyPheGlyGlyGlySerSerSerGlyGlyGlyTyrGlyGlyGlySer	conservative_inframe_insertion	Exon 7 of 8	1	NM_000421.5	ENSP00000269576.5	P13645
KRT10	ENST00000635956.2 link	c.1683_1684insAGCTCCGGCGGCGGATTCGGCGGCGGCAGCAGCTCCGGCGGCGGATACGGCGGCGGCAGC	p.Ser561_Ser562insSerSerGlyGlyGlyPheGlyGlyGlySerSerSerGlyGlyGlyTyrGlyGlyGlySer	conservative_inframe_insertion	Exon 7 of 8	2		ENSP00000490524.2	A0A1B0GVI3
KRT10-AS1	ENST00000301665.9 link	n.-250_-249insGCTGCCGCCGCCGTATCCGCCGCCGGAGCTGCTGCCGCCGCCGAATCCGCCGCCGGAGCT		upstream_gene_variant		2
KRT10-AS1	ENST00000436612.6 link	n.-251_-250insGCTGCCGCCGCCGTATCCGCCGCCGGAGCTGCTGCCGCCGCCGAATCCGCCGCCGGAGCT		upstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.00000765

AC:

AN:

130764

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000314

AC:

AN:

1275526

Hom.:

Cov.:

AF XY:

0.00000158

AC XY:

AN XY:

634512

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000599

Gnomad4 NFE exome

AF:

0.00000201

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000764

AC:

AN:

130866

Hom.:

Cov.:

AF XY:

0.0000157

AC XY:

AN XY:

63692

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000247

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over