This sequence change creates a premature translational stop signal (p.Glu556Glyfs*27) in the ABCD4 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 51 amino acid(s) of the ABCD4 protein. This variant is present in population databases (rs763777109, gnomAD 0.03%). This premature translational stop signal has been observed in individual(s) with cobalamin J disease (PMID: 28572511). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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_005050.4(ABCD4):c.1667_1668del (p.Glu556fs)
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.
Conflicting classifications of pathogenicity
Pathogenic(1); Uncertain significance(1)
Pathogenic(1); Uncertain significance(1)
2
criteria provided, conflicting classifications
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_005050.4(ABCD4):c.1667_1668del (p.Glu556fs)
Variation ID: 2137605 Accession: VCV002137605.2
- Type and length
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Microsatellite, 2 bp
- Location
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Cytogenetic: 14q24.3 14: 74286785-74286786 (GRCh38) [ NCBI UCSC ] 14: 74753488-74753489 (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 Feb 8, 2023 Mar 11, 2023 Oct 21, 2022 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_005050.4:c.1667_1668del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_005041.1:p.Glu556fs frameshift NM_001353591.2:c.1541_1542del NP_001340520.1:p.Glu514fs frameshift NM_001353592.2:c.1541_1542del NP_001340521.1:p.Glu514fs frameshift NM_001353593.2:c.1406_1407del NP_001340522.1:p.Glu469fs frameshift NM_001353594.2:c.1355_1356del NP_001340523.1:p.Glu452fs frameshift NM_001353595.2:c.1253_1254del NP_001340524.1:p.Glu418fs frameshift NM_001353596.2:c.1253_1254del NP_001340525.1:p.Glu418fs frameshift NM_001353597.2:c.1202_1203del NP_001340526.1:p.Glu401fs frameshift NM_001353598.2:c.1190_1191del NP_001340527.1:p.Glu397fs frameshift NM_001353599.2:c.1190_1191del NP_001340528.1:p.Glu397fs frameshift NM_001353600.2:c.1190_1191del NP_001340529.1:p.Glu397fs frameshift NM_001353601.2:c.1190_1191del NP_001340530.1:p.Glu397fs frameshift NM_001353602.2:c.878_879del NP_001340531.1:p.Glu293fs frameshift NM_001353603.2:c.878_879del NP_001340532.1:p.Glu293fs frameshift NM_001353604.2:c.878_879del NP_001340533.1:p.Glu293fs frameshift NM_001353605.2:c.878_879del NP_001340534.1:p.Glu293fs frameshift NM_001353606.2:c.878_879del NP_001340535.1:p.Glu293fs frameshift NM_001353607.2:c.878_879del NP_001340536.1:p.Glu293fs frameshift NM_001353608.2:c.878_879del NP_001340537.1:p.Glu293fs frameshift NM_001353609.2:c.878_879del NP_001340538.1:p.Glu293fs frameshift NM_001353610.2:c.*2AG[1] 3 prime UTR NM_020323.1:c.1536_1537AG[1] NP_064719.1:p.Glu513Glyfs frameshift NM_020324.3:c.1190_1191del NP_064720.1:p.Glu397fs frameshift NM_020325.3:c.1667_1668del NP_064730.1:p.Glu556fs frameshift NR_003256.3:n.1559AG[1] non-coding transcript variant NR_148466.2:n.1495AG[1] non-coding transcript variant NR_148467.2:n.1276AG[1] non-coding transcript variant NR_148468.2:n.1253AG[1] non-coding transcript variant NR_148469.2:n.1500AG[1] non-coding transcript variant NR_148470.2:n.1462AG[1] non-coding transcript variant NR_148471.2:n.1500AG[1] non-coding transcript variant NR_148472.2:n.1549AG[1] non-coding transcript variant NR_148473.2:n.1476AG[1] non-coding transcript variant NR_148474.2:n.1595AG[1] non-coding transcript variant NC_000014.9:g.74286785CT[1] NC_000014.8:g.74753488CT[1] NG_032875.1:g.21277AG[1] - Protein change
- E556fs, E293fs, E469fs, E401fs, E418fs, E397fs, E452fs, E514fs
- Other names
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- Canonical SPDI
- NC_000014.9:74286784:CTCT:CT
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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.
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- 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. |
|||
| ABCD4 | - | - |
GRCh38 GRCh37 |
430 | 452 | |
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. |
|---|---|---|---|---|
| Conflicting interpretations of pathogenicity (2) |
criteria provided, conflicting classifications
|
Oct 21, 2022 | RCV003062644.4 |
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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|---|---|---|---|---|---|
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Uncertain significance
(Aug 31, 2022)
|
criteria provided, single submitter
Method: clinical testing
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Methylmalonic acidemia with homocystinuria, type cblJ
Affected status: unknown
Allele origin:
germline
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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV003442351.1
First in ClinVar: Feb 07, 2023 Last updated: Feb 07, 2023 |
Comment:
This sequence change creates a premature translational stop signal (p.Glu556Glyfs*27) in the ABCD4 gene. While this is not anticipated to result in nonsense mediated decay, … (more)
This sequence change creates a premature translational stop signal (p.Glu556Glyfs*27) in the ABCD4 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 51 amino acid(s) of the ABCD4 protein. This variant is present in population databases (rs763777109, gnomAD 0.03%). This premature translational stop signal has been observed in individual(s) with cobalamin J disease (PMID: 28572511). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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)
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Pathogenic
(Oct 21, 2022)
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criteria provided, single submitter
Method: clinical testing
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Methylmalonic acidemia with homocystinuria, type cblJ
Affected status: unknown
Allele origin:
unknown
|
Baylor Genetics
Accession: SCV003835943.1
First in ClinVar: Mar 11, 2023 Last updated: Mar 11, 2023 |
|
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 creates a premature translational stop signal (p.Glu556Glyfs*27) in the ABCD4 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 51 amino acid(s) of the ABCD4 protein. This variant is present in population databases (rs763777109, gnomAD 0.03%). This premature translational stop signal has been observed in individual(s) with cobalamin J disease (PMID: 28572511). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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 |
|---|---|---|---|---|
| Clinical or ATPase domain mutations in ABCD4 disrupt the interaction between the vitamin B(12)-trafficking proteins ABCD4 and LMBD1. | Fettelschoss V | The Journal of biological chemistry | 2017 | PMID: 28572511 |
Text-mined citations for this variant ...
HelpRecord 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.