VCV000560306.3 - ClinVar

NM_173483.4(CYP4F22):c.242G>A (p.Gly81Asp)

Germline

Classification

criteria provided, single submitter. Learn more about how ClinVar calculates review status.

Pathogenic
Pathogenic (1)

1 out of 2 submissions contributed to this classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_173483.4(CYP4F22):c.242G>A (p.Gly81Asp)

Variation ID: 560306 Accession: VCV000560306.3

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 19p13.12 19: 15529728 (GRCh38) [ NCBI UCSC ] 19: 15640539 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Sep 8, 2018	Mar 16, 2025	Feb 17, 2025

HGVS

Nucleotide	Protein	Molecular consequence
NM_173483.4:c.242G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_775754.2:p.Gly81Asp	missense
NC_000019.10:g.15529728G>A
NC_000019.9:g.15640539G>A
NG_007987.1:g.26204G>A

Protein change

G81D

Other names

Canonical SPDI

NC_000019.10:15529727:G:A

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

The Genome Aggregation Database (gnomAD), exomes 0.00000

Links

ClinGen: CA305819020 dbSNP: rs369811073 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
CYP4F22		Gene associated with autosomal recessive phenotype	Not yet evaluated	GRCh38 GRCh37	315	333

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Autosomal recessive congenital ichthyosis 5	Pathogenic (1)	no assertion criteria provided	Apr 23, 2018	RCV000678397.2
Lamellar ichthyosis	Pathogenic (1)	criteria provided, single submitter	Feb 17, 2025	RCV005240452.1

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	Expand all rows Collapse all rows Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Pathogenic (Feb 17, 2025) C Contributing to aggregate classification	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Lamellar ichthyosis	Women's Health and Genetics/Laboratory Corporation of America, LabCorp Accession: SCV005886402.1 First in ClinVar: Mar 16, 2025 Last updated: Mar 16, 2025	Publications: PubMed (3) PubMed: 30011118‚ 33067036‚ 38588653 Comment: show Variant summary: CYP4F22 c.242G>A (p.Gly81Asp) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251438 control chromosomes. c.242G>A has been reported in the literature in individuals affected with Lamellar Ichthyosis (e.g. Hotz_2018, Diociaiuti_2024). These data indicate that the variant is likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function and found that the variant results in <10% of WT enzyme activity (Nohara_2021). The following publications have been ascertained in the context of this evaluation (PMID: 30011118, 38588653, 33067036). ClinVar contains an entry for this variant (Variation ID: 560306). Based on the evidence outlined above, the variant was classified as pathogenic. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Pathogenic (Apr 23, 2018) N Not contributing to aggregate classification	no assertion criteria provided	Autosomal recessive congenital ichthyosis 5	Institute for Human Genetics, University Medical Center Freiburg Accession: SCV000804468.1 First in ClinVar: Sep 08, 2018 Last updated: Sep 08, 2018	Publications: PubMed (1) PubMed: 30011118 Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes

Comment:

Variant summary: CYP4F22 c.242G>A (p.Gly81Asp) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251438 control chromosomes. c.242G>A has been reported in the literature in individuals affected with Lamellar Ichthyosis (e.g. Hotz_2018, Diociaiuti_2024). These data indicate that the variant is likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function and found that the variant results in <10% of WT enzyme activity (Nohara_2021). The following publications have been ascertained in the context of this evaluation (PMID: 30011118, 38588653, 33067036). ClinVar contains an entry for this variant (Variation ID: 560306). Based on the evidence outlined above, the variant was classified as pathogenic.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Cross-Sectional Study on Autosomal Recessive Congenital Ichthyoses: Association of Genotype with Disease Severity, Phenotypic, and Ultrastructural Features in 74 Italian Patients.	Diociaiuti A	Dermatology (Basel, Switzerland)	2024	PMID: 38588653
Impaired production of the skin barrier lipid acylceramide by CYP4F22 ichthyosis mutations.	Nohara T	Journal of dermatological science	2021	PMID: 33067036
Mutation update for CYP4F22 variants associated with autosomal recessive congenital ichthyosis.	Hotz A	Human mutation	2018	PMID: 30011118

Text-mined citations for rs369811073 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated May 17, 2025