rs150962030
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP3BP4
The NM_001004320.2(AGMO):c.653C>T(p.Pro218Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00021 in 1,612,192 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Genomes: 𝑓 0.0012 ( 0 hom., cov: 31)
Exomes 𝑓: 0.00010 ( 0 hom. )
Consequence
AGMO
NM_001004320.2 missense
NM_001004320.2 missense
Scores
13
4
2
Clinical Significance
Conservation
PhyloP100: 5.53
Genes affected
AGMO (HGNC:33784): (alkylglycerol monooxygenase) The protein encoded by this gene is a tetrahydrobiopterin- and iron-dependent enzyme that cleaves the ether bond of alkylglycerols. Sequence comparisons distinguish this protein as forming a third, distinct class of tetrahydrobiopterin-dependent enzymes. Variations in this gene have been associated with decreased glucose-stimulated insulin response, type 2 diabetes, and susceptibility to intracranial aneurysms. [provided by RefSeq, Aug 2012]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
Multiple lines of computational evidence support a deleterious effect 7: AlphaMissense, BayesDel_noAF, Cadd, Eigen, MutationAssessor, PROVEAN, REVEL [when max_spliceai, FATHMM_MKL, MetaRNN, MutationTaster was below the threshold]
BP4
Computational evidence support a benign effect (MetaRNN=0.32951206).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
AGMO | NM_001004320.2 | c.653C>T | p.Pro218Leu | missense_variant | 6/13 | ENST00000342526.8 | NP_001004320.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
AGMO | ENST00000342526.8 | c.653C>T | p.Pro218Leu | missense_variant | 6/13 | 1 | NM_001004320.2 | ENSP00000341662 | P1 | |
AGMO | ENST00000498264.1 | n.593C>T | non_coding_transcript_exon_variant | 2/2 | 5 |
Frequencies
GnomAD3 genomes AF: 0.00125 AC: 190AN: 152126Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.000239 AC: 60AN: 250940Hom.: 0 AF XY: 0.000170 AC XY: 23AN XY: 135626
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GnomAD4 exome AF: 0.000101 AC: 148AN: 1459948Hom.: 0 Cov.: 29 AF XY: 0.0000854 AC XY: 62AN XY: 726390
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GnomAD4 genome AF: 0.00125 AC: 190AN: 152244Hom.: 0 Cov.: 31 AF XY: 0.00107 AC XY: 80AN XY: 74428
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | May 24, 2017 | - - |
See cases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | New York Genome Center | Jun 01, 2020 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Pathogenic
D
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D
M_CAP
Uncertain
D
MetaRNN
Benign
T
MetaSVM
Pathogenic
D
MutationAssessor
Pathogenic
H
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D
REVEL
Pathogenic
Sift
Pathogenic
D
Sift4G
Pathogenic
D
Polyphen
D
Vest4
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
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