Genetic Variant NM_000421.5:c.1457_1458insAAGCTCCGGCGGCGGAAGCTCCGGCGGCGGAAGCT (chr17-40819077-G-GAGCTTCCGCCGCCGGAGCTTCCGCCGCCGGAGCTT) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000421.5(KRT10):c.1457_1458insAAGCTCCGGCGGCGGAAGCTCCGGCGGCGGAAGCT(p.His487SerfsTer144) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000206 in 145,864 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000021 ( 0 hom., cov: 31)

Consequence

KRT10
NM_000421.5 frameshift

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.66

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 made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRT10	NM_000421.5 link	c.1457_1458insAAGCTCCGGCGGCGGAAGCTCCGGCGGCGGAAGCT	p.His487SerfsTer144	frameshift_variant	Exon 7 of 8	ENST00000269576.6	NP_000412.4	P13645

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRT10	ENST00000269576.6 link	c.1457_1458insAAGCTCCGGCGGCGGAAGCTCCGGCGGCGGAAGCT	p.His487SerfsTer144	frameshift_variant	Exon 7 of 8	1	NM_000421.5	ENSP00000269576.5		P13645

Frequencies

GnomAD3 genomes

AF:

0.0000206

AC:

AN:

145864

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000766

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

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

Cov.:

GnomAD4 genome

AF:

0.0000206

AC:

AN:

145864

Hom.:

Cov.:

AF XY:

0.0000141

AC XY:

AN XY:

71108

show subpopulations

Gnomad4 AFR

AF:

0.0000766

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over