VCV000592165.6 - ClinVar

NM_145269.5(CIBAR1):c.478C>T (p.Arg160Ter)

Germline

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.

(3)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Pathogenic

criteria provided, single submitter

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_145269.5(CIBAR1):c.478C>T (p.Arg160Ter)

Variation ID: 592165 Accession: VCV000592165.6

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 8q22.1 8: 93709810 (GRCh38) [ NCBI UCSC ] 8: 94722038 (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	Feb 28, 2019	Jul 23, 2024	Apr 20, 2023

HGVS

Nucleotide	Protein	Molecular consequence
NM_145269.5:c.478C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_660312.2:p.Arg160Ter	nonsense
NM_001283034.2:c.478C>T	NP_001269963.1:p.Arg160Ter	nonsense
NR_104267.2:n.576C>T		non-coding transcript variant
NR_104268.2:n.576C>T		non-coding transcript variant
NR_156451.2:n.838C>T		non-coding transcript variant
NR_156452.2:n.760C>T		non-coding transcript variant
NR_156453.2:n.650C>T		non-coding transcript variant
NC_000008.11:g.93709810C>T
NC_000008.10:g.94722038C>T

... more HGVS ... less HGVS

Protein change

R160*

Other names

CIBAR1, ARG160TER (rs368652620)

Canonical SPDI

NC_000008.11:93709809:C:T

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

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.

Trans-Omics for Precision Medicine (TOPMed) 0.00000

The Genome Aggregation Database (gnomAD) 0.00001

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00008

Links

OMIM: 617273.0001 dbSNP: rs368652620 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.
CIBAR1		-	-	GRCh38 GRCh37	22	64

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.
Polydactyly, postaxial, type A9	Pathogenic (2)	criteria provided, single submitter	Apr 20, 2023	RCV000723368.6
Postaxial polydactyly type A	Likely pathogenic (1)	no assertion criteria provided	-	RCV001034603.1

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.	More information 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 (Apr 20, 2023)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Polydactyly, postaxial, type A9 Affected status: yes Allele origin: unknown	Institute of Human Genetics, University of Leipzig Medical Center Accession: SCV003925609.1 First in ClinVar: May 20, 2023 Last updated: May 20, 2023	Comment: This variant was identified as homozygous._x000D_ Criteria applied: PVS1, PM3, PM2_SUP
Pathogenic (Jul 12, 2024)	no assertion criteria provided Method: literature only	POLYDACTYLY, POSTAXIAL, TYPE A9 (1 family) Affected status: not provided Allele origin: germline	OMIM Accession: SCV000854768.5 First in ClinVar: Dec 10, 2018 Last updated: Jul 23, 2024	Publications: PubMed (1) PubMed: 30395363 Comment on evidence: In 3 Pakistani brothers with postaxial polydactyly type A9 (PAPA9; 618219), Schrauwen et al. (2018) identified homozygosity for a c.478C-T transition (c.478C-T, NM_001283034.1) in the … (more) In 3 Pakistani brothers with postaxial polydactyly type A9 (PAPA9; 618219), Schrauwen et al. (2018) identified homozygosity for a c.478C-T transition (c.478C-T, NM_001283034.1) in the FAM92A gene, resulting in an arg160-to-ter (R160X) substitution within the BAR domain. Their unaffected parents and an unaffected brother were heterozygous for the mutation, which was not found in 186 in-house Pakistani control DNA samples or in the Greater Middle East Variome Project database. However, the variant was present at a low frequency in the gnomAD database (all populations MAF, 2.04 x 10(-5); South East Asians MAF, 6.55 x 10(-5)). Experiments in transfected COS-7 cells demonstrated that both FAM92A homodimerization and the FAM92A/Chibby1 (CBY; 607757) complex were disrupted with the mutant protein. In addition, recruitment and colocalization of FAM92A with Chybby1 at the base of cilia was impaired with the R160X mutant compared to wildtype FAM92A. (less)
Likely pathogenic (-)	no assertion criteria provided Method: research	Nonsyndromic Postaxial Polydactyly Type A Affected status: yes Allele origin: inherited	University of Washington Center for Mendelian Genomics, University of Washington Accession: SCV001197983.1 First in ClinVar: Apr 15, 2020 Last updated: Apr 15, 2020	Publications: PubMed (1) PubMed: 30395363

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
FAM92A Underlies Nonsyndromic Postaxial Polydactyly in Humans and an Abnormal Limb and Digit Skeletal Phenotype in Mice.	Schrauwen I	Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research	2019	PMID: 30395363

Text-mined citations for rs368652620 ...

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 Jul 23, 2024

ClinVar Genomic variation as it relates to human health

NM_145269.5(CIBAR1):c.478C>T (p.Arg160Ter)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs368652620 ...