17-40818891-GCCGGAGCTGCCGCCC-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM4 BP6_Moderate

The NM_000421.5(KRT10):c.1629_1643del(p.Gly548_Ser552del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.000894 in 1,327,172 control chromosomes in the GnomAD database, including 25 homozygotes. Variant has been reported in ClinVar as Benign (★). Synonymous variant affecting the same amino acid position (i.e. G543G) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0016 (0 hom., cov: 23)
  • Exomes 𝑓: 0.00089 (25 hom.)
  • Failed GnomAD Quality Control
• Consequence: KRT10 NM_000421.5 inframe_deletion
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.93

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_000421.5.
• BP6: Variant 17-40818891-GCCGGAGCTGCCGCCC-G is Benign according to our data. Variant chr17-40818891-GCCGGAGCTGCCGCCC-G is described in ClinVar as [Benign]. Clinvar id is 3053465.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KRT10	NM_000421.5	c.1629_1643del	p.Gly548_Ser552del	inframe_deletion	7/8	ENST00000269576.6
KRT10	NM_001379366.1	c.1629_1643del	p.Gly548_Ser552del	inframe_deletion	7/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KRT10	ENST00000269576.6	c.1629_1643del	p.Gly548_Ser552del	inframe_deletion	7/8	1	NM_000421.5	P2
KRT10	ENST00000635956.2	c.1629_1643del	p.Gly548_Ser552del	inframe_deletion	7/8	2		A2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 235 AN: 150290 Hom.: 0 Cov.: 23 FAILED QC

Gnomad AFR AF: 0.00203

Gnomad AMI AF: 0.00442

Gnomad AMR AF: 0.00139

Gnomad ASJ AF: 0.000872

Gnomad EAS AF: 0.00292

Gnomad SAS AF: 0.00315

Gnomad FIN AF: 0.00145

Gnomad MID AF: 0.00321

Gnomad NFE AF: 0.00111

Gnomad OTH AF: 0.00146

GnomAD4 exome AF: 0.000894 AC: 1186 AN: 1327172 Hom.: 25 AF XY: 0.00106 AC XY: 698 AN XY: 657428

Gnomad4 AFR exome AF: 0.00320

Gnomad4 AMR exome AF: 0.00384

Gnomad4 ASJ exome AF: 0.00267

Gnomad4 EAS exome AF: 0.00176

Gnomad4 SAS exome AF: 0.00363

Gnomad4 FIN exome AF: 0.00159

Gnomad4 NFE exome AF: 0.000451

Gnomad4 OTH exome AF: 0.00102

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00156 AC: 235 AN: 150400 Hom.: 0 Cov.: 23 AF XY: 0.00164 AC XY: 121 AN XY: 73576

Gnomad4 AFR AF: 0.00203

Gnomad4 AMR AF: 0.00139

Gnomad4 ASJ AF: 0.000872

Gnomad4 EAS AF: 0.00293

Gnomad4 SAS AF: 0.00315

Gnomad4 FIN AF: 0.00145

Gnomad4 NFE AF: 0.00111

Gnomad4 OTH AF: 0.00144

Alfa AF: 0.0108 Hom.: 3

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

KRT10-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 29, 2019

This variant is classified as 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

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

Publications

LitVar

Other links and lift over

dbSNP: rs755330996; hg19: chr17-38975143;