ClinVar Genomic variation as it relates to human health
NM_052989.3(IFT122):c.349+5G>A
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.
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.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_052989.3(IFT122):c.349+5G>A
Variation ID: 4637 Accession: VCV000004637.9
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 3q21.3 3: 129461309 (GRCh38) [ NCBI UCSC ] 3: 129180152 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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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 Oct 2, 2013 Feb 14, 2024 Aug 10, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_052989.3:c.349+5G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
intron variant NM_001280541.2:c.502+5G>A intron variant NM_001280545.2:c.-102+5G>A intron variant NM_001280546.2:c.-102+5G>A intron variant NM_018262.4:c.349+5G>A intron variant NM_052985.4:c.502+5G>A intron variant NM_052990.3:c.194-2251G>A intron variant NC_000003.12:g.129461309G>A NC_000003.11:g.129180152G>A NG_023392.1:g.26185G>A - Protein change
- Other names
- IVS6, G-A, +5
- Canonical SPDI
- NC_000003.12:129461308:G:A
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe 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.
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD) 0.00004
Trans-Omics for Precision Medicine (TOPMed) 0.00005
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00015
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 | ||
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HI score
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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
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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. |
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IFT122 | - | - |
GRCh38 GRCh37 |
701 | 744 |
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
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The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Uncertain significance (4) |
criteria provided, multiple submitters, no conflicts
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Aug 10, 2023 | RCV000004900.11 |
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. |
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Uncertain significance
(May 26, 2022)
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criteria provided, single submitter
Method: clinical testing
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Cranioectodermal dysplasia 1
Affected status: unknown
Allele origin:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV002779400.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
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Uncertain significance
(Aug 10, 2023)
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criteria provided, single submitter
Method: clinical testing
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Cranioectodermal dysplasia 1
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV002206063.3
First in ClinVar: Mar 28, 2022 Last updated: Feb 14, 2024 |
Comment:
In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant … (more)
In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this variant results in skipping of exon 6 and introduces a premature termination codon (PMID: 20493458). The resulting mRNA is expected to undergo nonsense-mediated decay. ClinVar contains an entry for this variant (Variation ID: 4637). This variant has been observed in individual(s) with IFT122-related conditions (PMID: 20493458). This variant is present in population databases (rs376595844, gnomAD 0.004%). This sequence change falls in intron 6 of the IFT122 gene. It does not directly change the encoded amino acid sequence of the IFT122 protein. RNA analysis indicates that this variant induces altered splicing and may result in an absent or disrupted protein product. (less)
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Pathogenic
(Jun 11, 2010)
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no assertion criteria provided
Method: literature only
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CRANIOECTODERMAL DYSPLASIA 1
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000025076.2
First in ClinVar: Apr 04, 2013 Last updated: Jul 06, 2018 |
Comment on evidence:
In an Italian boy with cranioectodermal dysplasia (CED1; 218330), originally reported by Zaffanello et al. (2006), Walczak-Sztulpa et al. (2010) identified compound heterozygosity for a … (more)
In an Italian boy with cranioectodermal dysplasia (CED1; 218330), originally reported by Zaffanello et al. (2006), Walczak-Sztulpa et al. (2010) identified compound heterozygosity for a G-A transition in intron 6 (502+5G-A) of the IFT122 gene and a de novo trp7-to-cys substitution (W7C; 606045.0004) at a highly conserved residue in exon 1. The mother was a heterozygous carrier of the splice site mutation but the missense mutation was not detected in either parent; neither mutation was found in 340 ethnically matched control chromosomes. (less)
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not provided
(-)
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no classification provided
Method: literature only
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Cranioectodermal dysplasia 1
Affected status: not provided
Allele origin:
unknown
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GeneReviews
Accession: SCV000087024.2
First in ClinVar: Oct 02, 2013 Last updated: Oct 01, 2022 |
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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
HelpTitle | Author | Journal | Year | Link |
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Cranioectodermal Dysplasia. | Adam MP | - | 2022 | PMID: 24027799 |
Cranioectodermal Dysplasia, Sensenbrenner syndrome, is a ciliopathy caused by mutations in the IFT122 gene. | Walczak-Sztulpa J | American journal of human genetics | 2010 | PMID: 20493458 |
Aberrant 5' splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization. | Buratti E | Nucleic acids research | 2007 | PMID: 17576681 |
Sensenbrenner syndrome: a new member of the hepatorenal fibrocystic family. | Zaffanello M | American journal of medical genetics. Part A | 2006 | PMID: 17022080 |
Statistical features of human exons and their flanking regions. | Zhang MQ | Human molecular genetics | 1998 | PMID: 9536098 |
Text-mined citations for rs376595844 ...
HelpRecord last updated Feb 20, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.