chr16-53704185-A-G
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Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2
The NM_001080432.3(FTO):āc.1A>Gā(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 (ā ).
Frequency
Genomes: š 0.000013 ( 0 hom., cov: 32)
Exomes š: 0.0000021 ( 0 hom. )
Consequence
FTO
NM_001080432.3 start_lost
NM_001080432.3 start_lost
Scores
6
7
3
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
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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
DEOGEN2
Uncertain
.;T;T;.;T
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
PROVEAN
Benign
.;N;.;.;.
REVEL
Uncertain
Sift
Pathogenic
.;D;.;.;.
Sift4G
Pathogenic
.;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
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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