Genetic Variant NM_000421.5:c.1683_1684insAGCTCCGGCGGCGGATACGGCGGCGGCTGCAGCTCCGGCGGCGGATACGGCGGCGGCAGCAGCTCCGGCGGCGGATACGGCGGCGGCAGC (chr17-40818851-A-AGCTGCCGCCGCCGTATCCGCCGCCGGAGCTGCTGCCGCCGCCGTATCCGCCGCCGGAGCTGCAGCCGCCGCCGTATCCGCCGCCGGAGCT) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM4

The NM_000421.5(KRT10):c.1683_1684insAGCTCCGGCGGCGGATACGGCGGCGGCTGCAGCTCCGGCGGCGGATACGGCGGCGGCAGCAGCTCCGGCGGCGGATACGGCGGCGGCAGC(p.Ser561_Ser562insSerSerGlyGlyGlyTyrGlyGlyGlyCysSerSerGlyGlyGlyTyrGlyGlyGlySerSerSerGlyGlyGlyTyrGlyGlyGlySer) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000784 in 1,275,532 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.8e-7 ( 0 hom. )

Consequence

KRT10
NM_000421.5 conservative_inframe_insertion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0440

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_000421.5.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000421.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRT10	NM_000421.5	MANE Select	c.1683_1684insAGCTCCGGCGGCGGATACGGCGGCGGCTGCAGCTCCGGCGGCGGATACGGCGGCGGCAGCAGCTCCGGCGGCGGATACGGCGGCGGCAGC	p.Ser561_Ser562insSerSerGlyGlyGlyTyrGlyGlyGlyCysSerSerGlyGlyGlyTyrGlyGlyGlySerSerSerGlyGlyGlyTyrGlyGlyGlySer	conservative_inframe_insertion	Exon 7 of 8	NP_000412.4
	KRT10	NM_001379366.1		c.1683_1684insAGCTCCGGCGGCGGATACGGCGGCGGCTGCAGCTCCGGCGGCGGATACGGCGGCGGCAGCAGCTCCGGCGGCGGATACGGCGGCGGCAGC	p.Ser561_Ser562insSerSerGlyGlyGlyTyrGlyGlyGlyCysSerSerGlyGlyGlyTyrGlyGlyGlySerSerSerGlyGlyGlyTyrGlyGlyGlySer	conservative_inframe_insertion	Exon 7 of 8	NP_001366295.1	A0A1B0GVI3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KRT10	ENST00000269576.6	TSL:1 MANE Select	c.1683_1684insAGCTCCGGCGGCGGATACGGCGGCGGCTGCAGCTCCGGCGGCGGATACGGCGGCGGCAGCAGCTCCGGCGGCGGATACGGCGGCGGCAGC	p.Ser561_Ser562insSerSerGlyGlyGlyTyrGlyGlyGlyCysSerSerGlyGlyGlyTyrGlyGlyGlySerSerSerGlyGlyGlyTyrGlyGlyGlySer	conservative_inframe_insertion	Exon 7 of 8	ENSP00000269576.5	P13645
KRT10	ENST00000635956.2	TSL:2	c.1683_1684insAGCTCCGGCGGCGGATACGGCGGCGGCTGCAGCTCCGGCGGCGGATACGGCGGCGGCAGCAGCTCCGGCGGCGGATACGGCGGCGGCAGC	p.Ser561_Ser562insSerSerGlyGlyGlyTyrGlyGlyGlyCysSerSerGlyGlyGlyTyrGlyGlyGlySerSerSerGlyGlyGlyTyrGlyGlyGlySer	conservative_inframe_insertion	Exon 7 of 8	ENSP00000490524.2	A0A1B0GVI3
KRT10-AS1	ENST00000301665.10	TSL:2	n.-247_-246insGCTGCCGCCGCCGTATCCGCCGCCGGAGCTGCTGCCGCCGCCGTATCCGCCGCCGGAGCTGCAGCCGCCGCCGTATCCGCCGCCGGAGCT		upstream_gene	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.84e-7

AC:

AN:

1275532

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

634516

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25136

American (AMR)

AF:

0.00

AC:

AN:

38838

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23198

East Asian (EAS)

AF:

0.00

AC:

AN:

33126

South Asian (SAS)

AF:

0.00

AC:

AN:

70904

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33376

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4916

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

993778

Other (OTH)

AF:

0.0000191

AC:

AN:

52260

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.044

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over