Genetic Variant NM_000421.5:c.1450_1451insC (chr17-40819084-C-CG) – ACMG Classification: Pathogenic (10 pts)

Variant summary

Our verdict is Pathogenic. The variant received 10 ACMG points: 10P and 0B. PVS1PM2

The NM_000421.5(KRT10):c.1450_1451insC(p.Gly484AlafsTer97) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as not provided (no stars). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 31)

Consequence

KRT10
NM_000421.5 frameshift

Scores

Not classified

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: -0.00600

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: Pathogenic. The variant received 10 ACMG points.

PVS1

Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.

PM2

Very rare variant in population databases, with high coverage;

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KRT10	NM_000421.5	MANE Select	c.1450_1451insC	p.Gly484AlafsTer97	frameshift	Exon 7 of 8	NP_000412.4
KRT10	NM_001379366.1		c.1450_1451insC	p.Gly484AlafsTer97	frameshift	Exon 7 of 8	NP_001366295.1	A0A1B0GVI3
KRT10-AS1	NR_160886.1		n.-101_-100insG		upstream_gene	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KRT10	ENST00000269576.6	TSL:1 MANE Select	c.1450_1451insC	p.Gly484AlafsTer97	frameshift	Exon 7 of 8	ENSP00000269576.5	P13645
KRT10	ENST00000635956.2	TSL:2	c.1450_1451insC	p.Gly484AlafsTer97	frameshift	Exon 7 of 8	ENSP00000490524.2	A0A1B0GVI3
KRT10-AS1	ENST00000436612.7	TSL:2	n.14_15insG		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions as Germline

Significance:not provided

Revision:no classification provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.0060

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over