16-53826003-AA-GG

Variant names:

• chr16-53826003-AA-GG
• NM_001080432.3:c.263_264delAAinsGG
• FTO p.Lys88Arg

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001080432.3(FTO):​c.263_264delAAinsGG​(p.Lys88Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FTO NM_001080432.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.59
• Publications: 0 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: Orphanet, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FTO	NM_001080432.3	MANE Select	c.263_264delAAinsGG	p.Lys88Arg	missense	N/A	NP_001073901.1	Q9C0B1-1
	FTO	NM_001363894.2		c.263_264delAAinsGG	p.Lys88Arg	missense	N/A	NP_001350823.1
	FTO	NM_001363891.2		c.263_264delAAinsGG	p.Lys88Arg	missense	N/A	NP_001350820.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FTO	ENST00000471389.6	TSL:1 MANE Select	c.263_264delAAinsGG	p.Lys88Arg	missense	N/A	ENSP00000418823.1	Q9C0B1-1
	FTO	ENST00000637969.1	TSL:5	c.263_264delAAinsGG	p.Lys88Arg	missense	N/A	ENSP00000490516.1	A0A1B0GVH5
	FTO	ENST00000918264.1		c.263_264delAAinsGG	p.Lys88Arg	missense	N/A	ENSP00000588323.1

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		6.6

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr16-53859915;