rs115368866

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP7

The NM_001080432.3(FTO):​c.12C>A​(p.Thr4Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000005 in 1,399,178 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
Exomes 𝑓: 0.0000050 ( 0 hom. )

Consequence

FTO
NM_001080432.3 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.03
Variant links:
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 Likely_benign. Variant got -1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.41).
BP7
Synonymous conserved (PhyloP=-1.03 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FTONM_001080432.3 linkc.12C>A p.Thr4Thr synonymous_variant Exon 1 of 9 ENST00000471389.6 NP_001073901.1 Q9C0B1-1B3KU60Q99770

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FTOENST00000471389.6 linkc.12C>A p.Thr4Thr synonymous_variant Exon 1 of 9 1 NM_001080432.3 ENSP00000418823.1 Q9C0B1-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000500
AC:
7
AN:
1399178
Hom.:
0
Cov.:
30
AF XY:
0.00000435
AC XY:
3
AN XY:
690122
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000556
Gnomad4 OTH exome
AF:
0.0000172
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.41
CADD
Benign
10
DANN
Benign
0.86
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs115368866; hg19: chr16-53738108; API