rs3794261
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1
The NM_006838.4(METAP2):c.1095C>A(p.Thr365=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0865 in 1,606,536 control chromosomes in the GnomAD database, including 6,544 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.094 ( 705 hom., cov: 31)
Exomes 𝑓: 0.086 ( 5839 hom. )
Consequence
METAP2
NM_006838.4 synonymous
NM_006838.4 synonymous
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.356
Genes affected
METAP2 (HGNC:16672): (methionyl aminopeptidase 2) The protein encoded by this gene is a member of the methionyl aminopeptidase family. The encoded protein functions both by protecting the alpha subunit of eukaryotic initiation factor 2 from inhibitory phosphorylation and by removing the amino-terminal methionine residue from nascent proteins. Increased expression of this gene is associated with various forms of cancer, and the anti-cancer drugs fumagillin and ovalicin inhibit the protein by irreversibly binding to its active site. Inhibitors of this gene have also been shown to be effective for the treatment of obesity. A pseudogene of this gene is located on chromosome 2. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2015]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -11 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.22).
BP7
?
Synonymous conserved (PhyloP=-0.356 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.186 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
METAP2 | NM_006838.4 | c.1095C>A | p.Thr365= | synonymous_variant | 10/11 | ENST00000323666.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
METAP2 | ENST00000323666.10 | c.1095C>A | p.Thr365= | synonymous_variant | 10/11 | 1 | NM_006838.4 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.0939 AC: 14270AN: 151914Hom.: 709 Cov.: 31
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GnomAD3 exomes AF: 0.0940 AC: 23510AN: 250120Hom.: 1305 AF XY: 0.0927 AC XY: 12537AN XY: 135224
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GnomAD4 exome AF: 0.0857 AC: 124720AN: 1454504Hom.: 5839 Cov.: 29 AF XY: 0.0859 AC XY: 62147AN XY: 723828
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GnomAD4 genome ? AF: 0.0938 AC: 14265AN: 152032Hom.: 705 Cov.: 31 AF XY: 0.0937 AC XY: 6958AN XY: 74296
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ClinVar
Not reported inComputational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at