ClinVar Genomic variation as it relates to human health
NM_001368397.1(FRMPD4):c.2182G>C (p.Ala728Pro)
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_001368397.1(FRMPD4):c.2182G>C (p.Ala728Pro)
Variation ID: 985747 Accession: VCV000985747.7
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: Xp22.2 X: 12716641 (GRCh38) [ NCBI UCSC ] X: 12734760 (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 Nov 21, 2020 May 1, 2024 Jun 11, 2020 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001368397.1:c.2182G>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001355326.1:p.Ala728Pro missense NM_001368395.3:c.2293G>C NP_001355324.1:p.Ala765Pro missense NM_001368396.3:c.2188G>C NP_001355325.1:p.Ala730Pro missense NM_001368398.3:c.2293G>C NP_001355327.1:p.Ala765Pro missense NM_001368399.3:c.2173G>C NP_001355328.1:p.Ala725Pro missense NM_001368400.3:c.2062G>C NP_001355329.1:p.Ala688Pro missense NM_001368401.1:c.2158G>C NP_001355330.1:p.Ala720Pro missense NM_001368402.3:c.2158G>C NP_001355331.1:p.Ala720Pro missense NM_014728.3:c.2182G>C NP_055543.2:p.Ala728Pro missense NC_000023.11:g.12716641G>C NC_000023.10:g.12734760G>C NG_016419.3:g.899181G>C - Protein change
- A688P, A720P, A725P, A728P, A730P, A765P
- Other names
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- Canonical SPDI
- NC_000023.11:12716640:G:C
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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
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The frequency of the allele represented by this VCV record.
Trans-Omics for Precision Medicine (TOPMed) 0.00004
- Links
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
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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. |
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FRMPD4 | - | - |
GRCh38 GRCh37 |
307 | 484 |
Conditions - Germline
Condition
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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
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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 (1) |
criteria provided, single submitter
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Jan 15, 2020 | RCV001266814.4 | |
Uncertain significance (2) |
criteria provided, multiple submitters, no conflicts
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Jun 11, 2020 | RCV002471070.3 |
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
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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
(Jun 11, 2020)
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criteria provided, single submitter
Method: clinical testing
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Intellectual disability, X-linked 104
(X-linked recessive inheritance)
Affected status: yes
Allele origin:
germline
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Victorian Clinical Genetics Services, Murdoch Childrens Research Institute
Additional submitter:
Shariant Australia, Australian Genomics
Accession: SCV002768566.1
First in ClinVar: Dec 24, 2022 Last updated: Dec 24, 2022 |
Comment:
Based on the classification scheme VCGS_Germline_v1.1.1, this variant is classified as 3C-VUS. Following criteria are met: 0102 - Loss-of-function is a known mechanism of disease … (more)
Based on the classification scheme VCGS_Germline_v1.1.1, this variant is classified as 3C-VUS. Following criteria are met: 0102 - Loss-of-function is a known mechanism of disease for this gene. (N) 0109 - This gene is known to be associated with X-linked FRMPD4 -related intellectual disability. (N) 0200 - Variant is predicted to result in a missense amino acid change from an alanine to a proline (exon 15). (N) 0253 - Variant is hemizygous. (N) 0304 - Variant is present in gnomAD <0.01 for a recessive condition (3 heterozygotes, 0 hemizygotes). (P) 0309 - Multiple alternative amino acid changes at the same position have been observed in gnomAD (highest allele count: 19 heterozygotes, 5 hemizygotes). (N) 0503 - Missense variant consistently predicted to be tolerated and not conserved in mammals with a minor amino acid change. (B) 0604 - Variant is not located in an established domain, motif, hotspot or informative constraint region. (N) 0705 - A comparable variant has previously been classified as a VUS in ClinVar. (N) 0807 - Variant has not previously been reported in a clinical context. (N) 0905 - No segregation evidence has been identified for this variant. (N) 1007 - No published functional evidence has been identified for this variant in the literature. (N) 1208 - Inheritance information for this variant is not currently available. (N) Legend: (P) - Pathogenic, (N) - Neutral, (B) - Benign (less)
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Uncertain significance
(-)
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criteria provided, single submitter
Method: clinical testing
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Intellectual disability, X-linked 104
(X-linked inheritance)
Affected status: yes
Allele origin:
germline
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Neuberg Centre For Genomic Medicine, NCGM
Accession: SCV004047078.1
First in ClinVar: Oct 28, 2023 Last updated: Oct 28, 2023 |
Comment:
The missense variant p.Ala728Pro in FRMPD4 has been submitted to ClinVar as a Variant of Uncertain Significance, but no details are available for independent assessment. … (more)
The missense variant p.Ala728Pro in FRMPD4 has been submitted to ClinVar as a Variant of Uncertain Significance, but no details are available for independent assessment. The p.Ala728Pro variant is novel (not in any individuals) in 1000 Genomes and has allele frequency of 0.001462% in gnomAD database. The amino acid Ala at position 728 is changed to a Pro changing protein sequence and it might alter its composition and physico-chemical properties. The amino acid change p.Ala728Pro in FRMPD4 is predicted as conserved by PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Uncertain Significance (VUS) (less)
Clinical Features:
Neurodevelopmental delay (present) , Intellectual disability (present) , Hyperreflexia (present) , Hyperreflexia (present)
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Uncertain significance
(Jan 15, 2020)
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criteria provided, single submitter
Method: clinical testing
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Inborn genetic diseases
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV001444993.4
First in ClinVar: Nov 21, 2020 Last updated: May 01, 2024 |
Comment:
The alteration results in an amino acid change:_x000D_ _x000D_ The c.2182G>C (p.A728P) alteration is located in coding exon 15 of the FRMPD4 gene. This alteration … (more)
The alteration results in an amino acid change:_x000D_ _x000D_ The c.2182G>C (p.A728P) alteration is located in coding exon 15 of the FRMPD4 gene. This alteration results from a G to C substitution at nucleotide position 2182, causing the alanine (A) at amino acid position 728 to be replaced by a proline (P). The alteration has been observed in population databases: _x000D_ _x000D_ Based on data from the Genome Aggregation Database (gnomAD), the c.2182G>C alteration was observed in 0.0015%% (3/205,162) of total alleles studied. No hemizygotes were reported in gnomAD. The altered amino acid is not conserved throughout evolution:_x000D_ _x000D_ The p.A728 amino acid is not conserved in available vertebrate species. The alteration is predicted tolerated by in silico modeling:_x000D_ _x000D_ The p.A728P alteration is predicted to be tolerated by in silico analysis. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. (less)
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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
HelpThere are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar. |
Text-mined citations for rs750615873 ...
HelpRecord last updated May 01, 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.