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NM_000036.3(AMPD1):c.34C>T (p.Gln12Ter)

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Interpretation:
Conflicting interpretations of pathogenicity, other​

Benign(1);Pathogenic(1);Uncertain significance(3)

Review status:
criteria provided, conflicting interpretations
Submissions:
10 (Most recent: Nov 10, 2021)
Last evaluated:
Nov 1, 2021
Accession:
VCV000018271.11
Variation ID:
18271
Description:
single nucleotide variant
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NM_000036.3(AMPD1):c.34C>T (p.Gln12Ter)

Allele ID
33310
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
1p13.2
Genomic location
1: 114693436 (GRCh38) GRCh38 UCSC
1: 115236057 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000001.10:g.115236057G>A
NM_000036.2:c.133C>T NP_000027.2:p.Gln45Ter nonsense
NC_000001.11:g.114693436G>A
... more HGVS
Protein change
Q45*
Other names
Q12*
Canonical SPDI
NC_000001.11:114693435:G:A
Functional consequence
-
Global minor allele frequency (GMAF)
0.03814 (A)

Allele frequency
1000 Genomes Project 0.03814
Trans-Omics for Precision Medicine (TOPMed) 0.07788
Trans-Omics for Precision Medicine (TOPMed) 0.08070
The Genome Aggregation Database (gnomAD), exomes 0.08604
The Genome Aggregation Database (gnomAD) 0.08701
Exome Aggregation Consortium (ExAC) 0.08714
The Genome Aggregation Database (gnomAD) 0.09622
Links
ClinGen: CA128022
Genetic Testing Registry (GTR): GTR000503289
OMIM: 102770.0001
dbSNP: rs17602729
VarSome
Comment on variant
NCBI staff reviewed the sequence information reported in PubMed 1631143 Fig. 2A to determine the location of this allele on the current reference sequence.
NCBI staff reviewed the sequence information reported in PubMed 1631143 to determine the location of this allele on current reference sequence.
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Conflicting interpretations of pathogenicity 5 criteria provided, conflicting interpretations Oct 7, 2020 RCV000019933.37
Conflicting interpretations of pathogenicity, other 5 criteria provided, conflicting interpretations Nov 1, 2021 RCV000487355.7

Clinical features observed in individuals with this variant

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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
AMPD1 - - GRCh38
GRCh37
123 135

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Uncertain significance
(Nov 01, 2021)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV000568077.6
Submitted: (Nov 10, 2021)
Evidence details
Comment:
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This … (more)
other
(Feb 07, 2018)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics
Accession: SCV000854814.1
Submitted: (Sep 19, 2018)
Evidence details
Other databases
http://www.egl-eurofins.com/emvc…
Pathogenic
(Oct 23, 2020)
criteria provided, single submitter
Method: clinical testing
not provided
(Autosomal recessive inheritance)
Allele origin: germline
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen
Accession: SCV001446914.1
Submitted: (Oct 23, 2020)
Evidence details
Uncertain significance
(Mar 21, 2019)
criteria provided, single submitter
Method: clinical testing
Muscle AMP deaminase deficiency
Allele origin: unknown
Centre for Mendelian Genomics,University Medical Centre Ljubljana
Accession: SCV001366492.2
Submitted: (Nov 24, 2020)
Evidence details
Comment:
This variant was classified as: Uncertain significance. The available evidence favors the pathogenic nature of this variant, however the currently available data is insufficient to … (more)
Uncertain significance
(Oct 07, 2020)
criteria provided, single submitter
Method: clinical testing
Muscle AMP deaminase deficiency
Allele origin: germline
Invitae
Accession: SCV000755841.5
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (7)
Comment:
This sequence change creates a premature translational stop signal (p.Gln45*) in the AMPD1 gene. However, alternative splicing may rescue certain truncations, particularly those occurring in … (more)
Benign
(Jan 30, 2020)
criteria provided, single submitter
Method: clinical testing
Muscle AMP deaminase deficiency
Allele origin: germline
Al Jalila Children's Genomics Center,Al Jalila Childrens Speciality Hospital
Accession: SCV001984111.1
Submitted: (Oct 04, 2021)
Evidence details
Pathogenic
(Jun 01, 2011)
no assertion criteria provided
Method: literature only
MYOPATHY DUE TO MYOADENYLATE DEAMINASE DEFICIENCY
Allele origin: germline
OMIM
Accession: SCV000040231.4
Submitted: (Jul 03, 2014)
Evidence details
Publications
PubMed (2)
Pathogenic
(Feb 19, 2016)
no assertion criteria provided
Method: clinical testing
not provided
Allele origin: unknown
Mayo Clinic Laboratories, Mayo Clinic
Accession: SCV000802453.1
Submitted: (May 23, 2018)
Evidence details
Uncertain significance
(-)
no assertion criteria provided
Method: clinical testing
not provided
Allele origin: unknown
Department of Pathology and Laboratory Medicine,Sinai Health System
Additional submitter:
Franklin by Genoox
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV001551404.1
Submitted: (Mar 31, 2021)
Evidence details
Comment:
The AMPD1 p.Gln45* variant has been reported in multiple homozygous individuals with AMPD deficiency but has also been reported in multiple healthy controls, including athletes … (more)
not provided
(-)
no assertion provided
Method: phenotyping only
Muscle AMP deaminase deficiency
Allele origin: unknown
GenomeConnect, ClinGen
Accession: SCV000607345.1
Submitted: (Aug 22, 2017)
Evidence details
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)

Functional evidence

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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 this variant

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Title Author Journal Year Link
Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria. Nykamp K Genetics in medicine : official journal of the American College of Medical Genetics 2017 PMID: 28492532
Pathogenic variant burden in the ExAC database: an empirical approach to evaluating population data for clinical variant interpretation. Kobayashi Y Genome medicine 2017 PMID: 28166811
Primary adenosine monophosphate (AMP) deaminase deficiency in a hypotonic infant. Castro-Gago M Journal of child neurology 2011 PMID: 21343608
[Myoadenylate deaminase deficiency in a child with myalgias induced by physical exercise]. Pantoja-Martínez J Revista de neurologia 2004 PMID: 15378456
Myoadenylate deaminase deficiency with severe rhabdomyolysis. Baumeister FA European journal of pediatrics 1993 PMID: 8335021
Molecular basis of AMP deaminase deficiency in skeletal muscle. Morisaki T Proceedings of the National Academy of Sciences of the United States of America 1992 PMID: 1631143
Exon recognition and nucleocytoplasmic partitioning determine AMPD1 alternative transcript production. Mineo I Molecular and cellular biology 1991 PMID: 1922051
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=AMPD1 - - - -

Text-mined citations for rs17602729...

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These 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 Nov 27, 2021