17-40819089-GCTT-G

Variant names:

• chr17-40819089-GCTT-G
• rs778345104
• NM_000421.5:c.1443_1445delAAG

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 1P and 1B. PM4_Supporting BP6

The NM_000421.5(KRT10):​c.1443_1445delAAG​(p.Ser482del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000637 in 1,442,054 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (no stars). Synonymous variant affecting the same amino acid position (i.e. G481G) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0018 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00050 (0 hom.)
• Consequence: KRT10 NM_000421.5 disruptive_inframe_deletion
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -1.33

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-AS1 (HGNC:28305): (KRT10 antisense RNA 1) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_000421.5. Strenght limited to Supporting due to length of the change: 1aa.
• BP6: Variant 17-40819089-GCTT-G is Benign according to our data. Variant chr17-40819089-GCTT-G is described in ClinVar as [Likely_benign]. Clinvar id is 3050459.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRT10	NM_000421.5	c.1443_1445delAAG	p.Ser482del	disruptive_inframe_deletion	Exon 7 of 8	ENST00000269576.6	NP_000412.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRT10	ENST00000269576.6	c.1443_1445delAAG	p.Ser482del	disruptive_inframe_deletion	Exon 7 of 8	1	NM_000421.5	ENSP00000269576.5

Frequencies

GnomAD3 genomes AF: 0.00182 AC: 272 AN: 149648 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00501

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000997

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00118

Gnomad SAS AF: 0.00299

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000372

Gnomad OTH AF: 0.00389

GnomAD3 exomes AF: 0.000612 AC: 59 AN: 96464 Hom.: 0 AF XY: 0.000648 AC XY: 36 AN XY: 55588

Gnomad AFR exome AF: 0.00289

Gnomad AMR exome AF: 0.000317

Gnomad ASJ exome AF: 0.000140

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00180

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000366

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000499 AC: 645 AN: 1292304 Hom.: 0 AF XY: 0.000516 AC XY: 329 AN XY: 637804

Gnomad4 AFR exome AF: 0.00597

Gnomad4 AMR exome AF: 0.000523

Gnomad4 ASJ exome AF: 0.0000872

Gnomad4 EAS exome AF: 0.000540

Gnomad4 SAS exome AF: 0.00218

Gnomad4 FIN exome AF: 0.0000934

Gnomad4 NFE exome AF: 0.000223

Gnomad4 OTH exome AF: 0.00112

GnomAD4 genome AF: 0.00182 AC: 273 AN: 149750 Hom.: 0 Cov.: 31 AF XY: 0.00187 AC XY: 137 AN XY: 73130

Gnomad4 AFR AF: 0.00502

Gnomad4 AMR AF: 0.000996

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00118

Gnomad4 SAS AF: 0.00299

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000372

Gnomad4 OTH AF: 0.00385

Alfa AF: 0.000122 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

KRT10-related disorder Benign:1

Feb 01, 2024

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

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

LitVar

Other links and lift over

dbSNP: rs778345104; hg19: chr17-38975341;