This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 318 of the APTX protein (p.Arg318His). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with APTX-related conditions. ClinVar contains an entry for this variant (Variation ID: 286950). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The histidine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. 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.
ClinVar Genomic variation as it relates to human health
NM_001195248.2(APTX):c.953G>A (p.Arg318His)
Germline
Classification
Help
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.
(2)
Help
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.
Uncertain significance
2
criteria provided, multiple submitters, no conflicts
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_001195248.2(APTX):c.953G>A (p.Arg318His)
Variation ID: 286950 Accession: VCV000286950.5
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 9p21.1 9: 32973574 (GRCh38) [ NCBI UCSC ] 9: 32973572 (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 Dec 6, 2016 Feb 7, 2023 Feb 17, 2022 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_001195248.2:c.953G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001182177.2:p.Arg318His missense NM_001195249.2:c.953G>A NP_001182178.1:p.Arg318His missense NM_001195250.2:c.791G>A NP_001182179.2:p.Arg264His missense NM_001195251.2:c.*110G>A 3 prime UTR NM_001195252.2:c.737G>A NP_001182181.2:p.Arg246His missense NM_001195254.2:c.791G>A NP_001182183.1:p.Arg264His missense NM_001368995.1:c.953G>A NP_001355924.1:p.Arg318His missense NM_001368996.1:c.953G>A NP_001355925.1:p.Arg318His missense NM_001368997.1:c.953G>A NP_001355926.1:p.Arg318His missense NM_001368998.1:c.953G>A NP_001355927.1:p.Arg318His missense NM_001368999.1:c.*110G>A 3 prime UTR NM_001369000.1:c.791G>A NP_001355929.1:p.Arg264His missense NM_001369001.1:c.791G>A NP_001355930.1:p.Arg264His missense NM_001369002.1:c.689G>A NP_001355931.1:p.Arg230His missense NM_001369003.1:c.689G>A NP_001355932.1:p.Arg230His missense NM_001369004.1:c.689G>A NP_001355933.1:p.Arg230His missense NM_001369005.1:c.689G>A NP_001355934.1:p.Arg230His missense NM_001369006.1:c.*110G>A 3 prime UTR NM_001370669.1:c.689G>A NP_001357598.1:p.Arg230His missense NM_001370670.1:c.689G>A NP_001357599.1:p.Arg230His missense NM_001370673.1:c.689G>A NP_001357602.1:p.Arg230His missense NM_175069.3:c.*110G>A 3 prime UTR NM_175073.3:c.953G>A NP_778243.1:p.Arg318His missense NR_036577.2:n.904G>A non-coding transcript variant NR_160920.1:n.792G>A non-coding transcript variant NR_160921.1:n.923G>A non-coding transcript variant NR_160922.1:n.1154G>A non-coding transcript variant NR_160923.1:n.958G>A non-coding transcript variant NR_160924.1:n.963G>A non-coding transcript variant NR_160925.1:n.1159G>A non-coding transcript variant NR_160926.1:n.949G>A non-coding transcript variant NR_160927.1:n.1042G>A non-coding transcript variant NR_160928.1:n.968G>A non-coding transcript variant NR_160929.1:n.846G>A non-coding transcript variant NR_160930.1:n.899G>A non-coding transcript variant NR_160931.1:n.1138G>A non-coding transcript variant NC_000009.12:g.32973574C>T NC_000009.11:g.32973572C>T NG_012821.2:g.56558G>A - Protein change
- R318H, R246H, R264H, R230H
- Other names
- -
- Canonical SPDI
- NC_000009.12:32973573:C:T
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- -
-
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.
- -
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
-
Exome Aggregation Consortium (ExAC) 0.00002
The Genome Aggregation Database (gnomAD), exomes 0.00003
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00008
Trans-Omics for Precision Medicine (TOPMed) 0.00012
- 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 | ||
|---|---|---|---|---|---|---|
| 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. |
|||
| APTX | - | - |
GRCh38 GRCh37 |
289 | 358 | |
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. |
|---|---|---|---|---|
| Uncertain significance (2) |
criteria provided, multiple submitters, no conflicts
|
Feb 17, 2022 | RCV000351313.6 |
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. |
|
|---|---|---|---|---|---|
|
Uncertain significance
(Apr 26, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Eurofins Ntd Llc (ga)
Accession: SCV000340555.4
First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016 |
Number of individuals with the variant: 1
Sex: mixed
|
|
|
Uncertain significance
(Feb 17, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV002996601.1
First in ClinVar: Feb 07, 2023 Last updated: Feb 07, 2023 |
Comment:
This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 318 of the APTX protein (p.Arg318His). … (more)
This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 318 of the APTX protein (p.Arg318His). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with APTX-related conditions. ClinVar contains an entry for this variant (Variation ID: 286950). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The histidine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. 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. (less)
|
Comment:
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. |
Comment:
This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 318 of the APTX protein (p.Arg318His). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with APTX-related conditions. ClinVar contains an entry for this variant (Variation ID: 286950). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The histidine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. 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.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=APTX | - | - | - | - |
Text-mined citations for rs371292546 ...
HelpThese 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 Sep 29, 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.