chr17-41567438-CCCACTTCCTCCTCCAGAGCCACTTCCTCCTCCATAGTTGCCCCCACTTCCTCCACTATGACCACCTCCACTTCCTCCGCTATGGCCACCTCCACTTCCTCCACCATAGCCACCTCCACTACCTCCTCCAGAACCACTTCCTCCACCGTAGCTGCCTCCACTTCCTCCCCTGGACCCACTTCCTCCACCATAGCCACCT-C

Position:

• chr17-41567438-CCCACTTCCTCCTCCAGAGCCACTTCCTCCTCCATAGTTGCCCCCACTTCCTCCACTATGACCACCTCCACTTCCTCCGCTATGGCCACCTCCACTTCCTCCACCATAGCCACCTCCACTACCTCCTCCAGAACCACTTCCTCCACCGTAGCTGCCTCCACTTCCTCCCCTGGACCCACTTCCTCCACCATAGCCACCT-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_000226.4(KRT9):​c.1509_1706del​(p.Gly504_Gly569del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000772 in 129,498 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0000077 (0 hom., cov: 31)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: KRT9 NM_000226.4 disruptive_inframe_deletion
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.83

Genes affected

KRT9 (HGNC:6447): (keratin 9) This gene encodes the type I keratin 9, an intermediate filament chain expressed only in the terminally differentiated epidermis of palms and soles. Mutations in this gene cause epidermolytic palmoplantar keratoderma. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 17-41567438-CCCACTTCCTCCTCCAGAGCCACTTCCTCCTCCATAGTTGCCCCCACTTCCTCCACTATGACCACCTCCACTTCCTCCGCTATGGCCACCTCCACTTCCTCCACCATAGCCACCTCCACTACCTCCTCCAGAACCACTTCCTCCACCGTAGCTGCCTCCACTTCCTCCCCTGGACCCACTTCCTCCACCATAGCCACCT-C is Benign according to our data. Variant chr17-41567438-CCCACTTCCTCCTCCAGAGCCACTTCCTCCTCCATAGTTGCCCCCACTTCCTCCACTATGACCACCTCCACTTCCTCCGCTATGGCCACCTCCACTTCCTCCACCATAGCCACCTCCACTACCTCCTCCAGAACCACTTCCTCCACCGTAGCTGCCTCCACTTCCTCCCCTGGACCCACTTCCTCCACCATAGCCACCT-C is described in ClinVar as [Benign]. Clinvar id is 1622183.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRT9	NM_000226.4	c.1509_1706del	p.Gly504_Gly569del	disruptive_inframe_deletion	7/8	ENST00000246662.9	NP_000217.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRT9	ENST00000246662.9	c.1509_1706del	p.Gly504_Gly569del	disruptive_inframe_deletion	7/8	1	NM_000226.4	ENSP00000246662.4
KRT9	ENST00000588431.1	c.810_1007del	p.Gly271_Gly336del	disruptive_inframe_deletion	8/9	1		ENSP00000467932.1

Frequencies

GnomAD3 genomes AF: 0.00000772 AC: 1 AN: 129498 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000249

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 7.15e-7 AC: 1 AN: 1398472 Hom.: 0 AF XY: 0.00000145 AC XY: 1 AN XY: 691002

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000124

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00000772 AC: 1 AN: 129498 Hom.: 0 Cov.: 31 AF XY: 0.0000158 AC XY: 1 AN XY: 63188

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000249

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Nov 26, 2023

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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: rs1906909104; hg19: chr17-39723690;