NM_001080432.3:c.1239+8577A>G

Variant names:

• chr16-53897528-A-G
• rs13335343
• NM_001080432.3:c.1239+8577A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001080432.3(FTO):​c.1239+8577A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.835 in 152,184 control chromosomes in the GnomAD database, including 54,104 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 0.84 (54104 hom., cov: 33)
• Consequence: FTO NM_001080432.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0590
• Publications: 4 publications found

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]

FTO Gene-Disease associations (from GenCC):

• lethal polymalformative syndrome, Boissel type

  Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.907 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080432.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FTO	NM_001080432.3	MANE Select	c.1239+8577A>G		intron	N/A	NP_001073901.1
	FTO	NM_001363894.2		c.1240-3112A>G		intron	N/A	NP_001350823.1
	FTO	NM_001363891.2		c.1269+8577A>G		intron	N/A	NP_001350820.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FTO	ENST00000471389.6	TSL:1 MANE Select	c.1239+8577A>G		intron	N/A	ENSP00000418823.1
	FTO	ENST00000637969.1	TSL:5	c.1239+8577A>G		intron	N/A	ENSP00000490516.1
	FTO	ENST00000637001.1	TSL:5	c.1239+8577A>G		intron	N/A	ENSP00000489936.1

Frequencies

GnomAD3 genomes AF: 0.835 AC: 127051 AN: 152066 Hom.: 54083 Cov.: 33

Gnomad AFR AF: 0.649

Gnomad AMI AF: 0.966

Gnomad AMR AF: 0.900

Gnomad ASJ AF: 0.956

Gnomad EAS AF: 0.866

Gnomad SAS AF: 0.824

Gnomad FIN AF: 0.903

Gnomad MID AF: 0.930

Gnomad NFE AF: 0.913

Gnomad OTH AF: 0.873

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.835 AC: 127114 AN: 152184 Hom.: 54104 Cov.: 33 AF XY: 0.837 AC XY: 62233 AN XY: 74392

African (AFR) AF: 0.649 AC: 26898 AN: 41468

American (AMR) AF: 0.900 AC: 13751 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.956 AC: 3318 AN: 3472

East Asian (EAS) AF: 0.866 AC: 4491 AN: 5186

South Asian (SAS) AF: 0.825 AC: 3980 AN: 4826

European-Finnish (FIN) AF: 0.903 AC: 9584 AN: 10614

Middle Eastern (MID) AF: 0.925 AC: 272 AN: 294

European-Non Finnish (NFE) AF: 0.913 AC: 62090 AN: 68026

Other (OTH) AF: 0.875 AC: 1849 AN: 2112

Alfa AF: 0.865 Hom.: 25428

Bravo AF: 0.827

Asia WGS AF: 0.851 AC: 2960 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.2
DANN	Benign	0.42
PhyloP100		-0.059
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs13335343; hg19: chr16-53931440;