chr16-53704185-A-G
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2
The NM_001080432.3(FTO):c.1A>G(p.Met1?) variant causes a start lost change. The variant allele was found at a frequency of 0.00000322 in 1,551,548 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Consequence
FTO
NM_001080432.3 start_lost
NM_001080432.3 start_lost
Scores
4
5
2
Clinical Significance
Conservation
PhyloP100: 5.12
Genes affected
FTO (HGNC:24678): (FTO alpha-ketoglutarate dependent dioxygenase) This gene is a nuclear protein of the AlkB related non-haem iron and 2-oxoglutarate-dependent oxygenase superfamily but the exact physiological function of this gene is not known. Other non-heme iron enzymes function to reverse alkylated DNA and RNA damage by oxidative demethylation. Studies in mice and humans indicate a role in nervous and cardiovascular systems and a strong association with body mass index, obesity risk, and type 2 diabetes. [provided by RefSeq, Jul 2011]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 10 ACMG points.
PVS1
?
Start lost variant, no new inframe start found.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FTO | NM_001080432.3 | c.1A>G | p.Met1? | start_lost | 1/9 | ENST00000471389.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FTO | ENST00000471389.6 | c.1A>G | p.Met1? | start_lost | 1/9 | 1 | NM_001080432.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152230Hom.: 0 Cov.: 32
GnomAD3 genomes
?
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32
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GnomAD4 exome AF: 0.00000214 AC: 3AN: 1399200Hom.: 0 Cov.: 30 AF XY: 0.00000290 AC XY: 2AN XY: 690124
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GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152348Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74502
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Lethal polymalformative syndrome, Boissel type Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Dec 26, 2022 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Uncertain
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Pathogenic
FATHMM_MKL
Benign
D
LIST_S2
Uncertain
D;D;D;D;D
M_CAP
Pathogenic
D
MetaRNN
Uncertain
D;D;D;D;D
MetaSVM
Uncertain
T
MutationTaster
Benign
D;D
Polyphen
0.97
.;D;.;.;.
Vest4
0.95
MutPred
Loss of catalytic residue at M1 (P = 0.0103);Loss of catalytic residue at M1 (P = 0.0103);Loss of catalytic residue at M1 (P = 0.0103);Loss of catalytic residue at M1 (P = 0.0103);Loss of catalytic residue at M1 (P = 0.0103);
MVP
0.85
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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