ClinVar Genomic variation as it relates to human health
NM_001370658.1(BTD):c.68A>G (p.His23Arg)
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.
Uncertain significance(3); Likely benign(1)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_001370658.1(BTD):c.68A>G (p.His23Arg)
Variation ID: 38483 Accession: VCV000038483.13
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 3p25.1 3: 15635507 (GRCh38) [ NCBI UCSC ] 3: 15677014 (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 14, 2017 May 1, 2024 Oct 24, 2022 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001370658.1:c.68A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001357587.1:p.His23Arg missense NM_000060.4:c.128A>G NP_000051.1:p.His43Arg missense NM_001281723.4:c.68A>G NP_001268652.2:p.His23Arg missense NM_001281724.3:c.68A>G NP_001268653.2:p.His23Arg missense NM_001281725.3:c.68A>G NP_001268654.1:p.His23Arg missense NM_001281726.3:c.68A>G NP_001268655.2:p.His23Arg missense NM_001323582.2:c.68A>G NP_001310511.1:p.His23Arg missense NM_001370752.1:c.68A>G NP_001357681.1:p.His23Arg missense NM_001370753.1:c.68A>G NP_001357682.1:p.His23Arg missense NM_001407364.1:c.68A>G NP_001394293.1:p.His23Arg missense NM_001407365.1:c.68A>G NP_001394294.1:p.His23Arg missense NM_001407366.1:c.68A>G NP_001394295.1:p.His23Arg missense NM_001407367.1:c.68A>G NP_001394296.1:p.His23Arg missense NM_001407368.1:c.68A>G NP_001394297.1:p.His23Arg missense NM_001407369.1:c.68A>G NP_001394298.1:p.His23Arg missense NM_001407370.1:c.68A>G NP_001394299.1:p.His23Arg missense NM_001407371.1:c.68A>G NP_001394300.1:p.His23Arg missense NM_001407372.1:c.68A>G NP_001394301.1:p.His23Arg missense NM_001407373.1:c.68A>G NP_001394302.1:p.His23Arg missense NM_001407374.1:c.68A>G NP_001394303.1:p.His23Arg missense NM_001407375.1:c.68A>G NP_001394304.1:p.His23Arg missense NM_001407376.1:c.68A>G NP_001394305.1:p.His23Arg missense NM_001407377.1:c.68A>G NP_001394306.1:p.His23Arg missense NM_001407378.1:c.68A>G NP_001394307.1:p.His23Arg missense NM_001407379.1:c.68A>G NP_001394308.1:p.His23Arg missense NM_001407380.1:c.68A>G NP_001394309.1:p.His23Arg missense NM_001407381.1:c.68A>G NP_001394310.1:p.His23Arg missense NM_001407382.1:c.68A>G NP_001394311.1:p.His23Arg missense NM_001407383.1:c.68A>G NP_001394312.1:p.His23Arg missense NM_001407384.1:c.68A>G NP_001394313.1:p.His23Arg missense NM_001407386.1:c.68A>G NP_001394315.1:p.His23Arg missense NM_001407388.1:c.68A>G NP_001394317.1:p.His23Arg missense NM_001407390.1:c.68A>G NP_001394319.1:p.His23Arg missense NM_001407392.1:c.68A>G NP_001394321.1:p.His23Arg missense NM_001407394.1:c.68A>G NP_001394323.1:p.His23Arg missense NM_001407395.1:c.68A>G NP_001394324.1:p.His23Arg missense NM_001407396.1:c.68A>G NP_001394325.1:p.His23Arg missense NM_001407397.1:c.68A>G NP_001394326.1:p.His23Arg missense NM_001407398.1:c.68A>G NP_001394327.1:p.His23Arg missense NM_001407399.1:c.68A>G NP_001394328.1:p.His23Arg missense NM_001407400.1:c.68A>G NP_001394329.1:p.His23Arg missense NM_001407401.1:c.68A>G NP_001394330.1:p.His23Arg missense NC_000003.12:g.15635507A>G NC_000003.11:g.15677014A>G NG_008019.2:g.39156A>G - Protein change
- H23R
- Other names
- H43R
- Canonical SPDI
- NC_000003.12:15635506:A:G
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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.
Trans-Omics for Precision Medicine (TOPMed) 0.00033
Exome Aggregation Consortium (ExAC) 0.00035
The Genome Aggregation Database (gnomAD), exomes 0.00036
The Genome Aggregation Database (gnomAD) 0.00042
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00069
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
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. |
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BTD | - | - |
GRCh38 GRCh37 |
647 | 724 |
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. |
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Conflicting interpretations of pathogenicity (5) |
criteria provided, conflicting classifications
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Oct 24, 2022 | RCV000022030.19 | |
Uncertain significance (1) |
no assertion criteria provided
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Jan 1, 2019 | RCV001251701.9 | |
Uncertain significance (1) |
criteria provided, single submitter
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Jun 29, 2022 | RCV002513289.9 |
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
(Oct 24, 2022)
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criteria provided, single submitter
Method: clinical testing
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Biotinidase deficiency
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000943282.2
First in ClinVar: Aug 14, 2019 Last updated: Feb 07, 2023 |
Comment:
This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 43 of the BTD protein (p.His43Arg). … (more)
This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 43 of the BTD protein (p.His43Arg). This variant is present in population databases (rs146011150, gnomAD 0.07%). This missense change has been observed in individual(s) with a positive newborn screening result for BTD-related disease (PMID: 26810761). ClinVar contains an entry for this variant (Variation ID: 38483). 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 arginine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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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Uncertain significance
(Oct 22, 2022)
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criteria provided, single submitter
Method: clinical testing
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Biotinidase deficiency
Affected status: unknown
Allele origin:
unknown
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Baylor Genetics
Accession: SCV003835547.1
First in ClinVar: Mar 11, 2023 Last updated: Mar 11, 2023 |
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Likely benign
(Jan 01, 2019)
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criteria provided, single submitter
Method: clinical testing
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Biotinidase deficiency
Affected status: yes
Allele origin:
unknown
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Institute of Human Genetics, University of Leipzig Medical Center
Accession: SCV001440042.1
First in ClinVar: Oct 31, 2020 Last updated: Oct 31, 2020 |
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Uncertain significance
(Jun 29, 2022)
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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: SCV003698460.2
First in ClinVar: Feb 07, 2023 Last updated: May 01, 2024 |
Comment:
The c.128A>G (p.H43R) alteration is located in exon 2 (coding exon 2) of the BTD gene. This alteration results from a A to G substitution … (more)
The c.128A>G (p.H43R) alteration is located in exon 2 (coding exon 2) of the BTD gene. This alteration results from a A to G substitution at nucleotide position 128, causing the histidine (H) at amino acid position 43 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. (less)
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Uncertain significance
(Feb 04, 2020)
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no assertion criteria provided
Method: clinical testing
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Biotinidase deficiency
Affected status: unknown
Allele origin:
germline
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Natera, Inc.
Accession: SCV001454447.1
First in ClinVar: Jan 02, 2021 Last updated: Jan 02, 2021 |
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Uncertain significance
(Jan 01, 2019)
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no assertion criteria provided
Method: clinical testing
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Intellectual disability
Affected status: yes
Allele origin:
unknown
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Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille
Accession: SCV001427442.1
First in ClinVar: Aug 17, 2020 Last updated: Aug 17, 2020 |
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not provided
(-)
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no classification provided
Method: phenotyping only
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Biotinidase deficiency
Affected status: unknown
Allele origin:
germline
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GenomeConnect, ClinGen
Accession: SCV000607107.1
First in ClinVar: Oct 14, 2017 Last updated: Oct 14, 2017 |
Comment:
GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical … (more)
GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. (less)
Clinical Features:
Decreased fetal movement (present) , Abnormal delivery (present) , Short stature (present) , Abnormality of the neck (present) , Oral-pharyngeal dysphagia (present) , Abnormality of … (more)
Decreased fetal movement (present) , Abnormal delivery (present) , Short stature (present) , Abnormality of the neck (present) , Oral-pharyngeal dysphagia (present) , Abnormality of eye movement (present) , Hypermetropia (present) , Ptosis (present) , Cognitive impairment (present) , Abnormality of coordination (present) , Generalized hypotonia (present) , Abnormality of digit (present) , Abnormality of facial musculature (present) , Abnormality of muscle physiology (present) , Abnormality of the musculature of the limbs (present) , Abnormality of the musculature of the thorax (present) , Abnormality of the musculature of the pelvis (present) , Feeding difficulties (present) , Abnormality of esophagus morphology (present) , Abnormality of the large intestine (present) (less)
Indication for testing: Diagnostic
Age: 0-9 years
Sex: female
Testing laboratory: Baylor Genetics
Date variant was reported to submitter: 2015-01-27
Testing laboratory interpretation: Uncertain significance
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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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Forty-eight novel mutations causing biotinidase deficiency. | Procter M | Molecular genetics and metabolism | 2016 | PMID: 26810761 |
Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. | Richards S | Genetics in medicine : official journal of the American College of Medical Genetics | 2015 | PMID: 25741868 |
Text-mined citations for rs146011150 ...
HelpRecord last updated May 08, 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.