rs61741025
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBP6
The NM_000036.3(AMPD1):c.334G>A(p.Val112Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00032 in 1,614,082 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.0016 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00019 ( 1 hom. )
Consequence
AMPD1
NM_000036.3 missense
NM_000036.3 missense
Scores
1
5
12
Clinical Significance
Conservation
PhyloP100: 7.71
Genes affected
AMPD1 (HGNC:468): (adenosine monophosphate deaminase 1) Adenosine monophosphate deaminase 1 catalyzes the deamination of AMP to IMP in skeletal muscle and plays an important role in the purine nucleotide cycle. Two other genes have been identified, AMPD2 and AMPD3, for the liver- and erythocyte-specific isoforms, respectively. Deficiency of the muscle-specific enzyme is apparently a common cause of exercise-induced myopathy and probably the most common cause of metabolic myopathy in the human. Alternatively spliced transcript variants encoding different isoforms have been identified in this gene.[provided by RefSeq, Feb 2010]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.012233764).
BP6
?
Variant 1-114686792-C-T is Benign according to our data. Variant chr1-114686792-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 197097.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=3, Benign=1, Uncertain_significance=1}.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AMPD1 | NM_000036.3 | c.334G>A | p.Val112Met | missense_variant | 4/16 | ENST00000520113.7 | |
AMPD1 | NM_001172626.2 | c.322G>A | p.Val108Met | missense_variant | 3/15 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AMPD1 | ENST00000520113.7 | c.334G>A | p.Val112Met | missense_variant | 4/16 | 1 | NM_000036.3 | P4 | |
AMPD1 | ENST00000369538.4 | c.322G>A | p.Val108Met | missense_variant | 3/15 | 2 | A1 | ||
AMPD1 | ENST00000485564.3 | n.208G>A | non_coding_transcript_exon_variant | 1/3 | 5 | ||||
AMPD1 | ENST00000637080.1 | c.337G>A | p.Val113Met | missense_variant, NMD_transcript_variant | 3/14 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00153 AC: 233AN: 152094Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000656 AC: 165AN: 251448Hom.: 0 AF XY: 0.000515 AC XY: 70AN XY: 135898
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GnomAD4 exome AF: 0.000189 AC: 276AN: 1461870Hom.: 1 Cov.: 32 AF XY: 0.000180 AC XY: 131AN XY: 727232
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GnomAD4 genome ? AF: 0.00158 AC: 240AN: 152212Hom.: 1 Cov.: 32 AF XY: 0.00141 AC XY: 105AN XY: 74428
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:4
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Oct 20, 2022 | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Likely benign, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Aug 28, 2017 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Mar 04, 2016 | - - |
Muscle AMP deaminase deficiency Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 21, 2024 | - - |
AMPD1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | May 20, 2020 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T;T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
M;.
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Vest4
MVP
MPC
ClinPred
T
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at