chr16-53994059-T-C

Variant names:

• chr16-53994059-T-C
• rs12596210
• NM_001080432.3:c.1364+59950T>C

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4 BA1

The NM_001080432.3(FTO):​c.1364+59950T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 152,194 control chromosomes in the GnomAD database, including 1,443 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 0.12 (1443 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: FTO NM_001080432.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.536
• Publications: 17 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

ENSG00000280392 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.14).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.253 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FTO	NM_001080432.3	MANE Select	c.1364+59950T>C		intron	N/A	NP_001073901.1	Q9C0B1-1
	FTO	NM_001363894.2		c.1427+59950T>C		intron	N/A	NP_001350823.1
	FTO	NM_001363891.2		c.1394+59950T>C		intron	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.1364+59950T>C		intron	N/A	ENSP00000418823.1	Q9C0B1-1
	FTO	ENST00000268349.7	TSL:1	c.97+9105T>C		intron	N/A	ENSP00000268349.7	X6R3I0
	FTO	ENST00000463855.1	TSL:1	c.230+59950T>C		intron	N/A	ENSP00000417843.1	Q9C0B1-2

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18466 AN: 152076 Hom.: 1435 Cov.: 32

Gnomad AFR AF: 0.0788

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.259

Gnomad ASJ AF: 0.0862

Gnomad EAS AF: 0.244

Gnomad SAS AF: 0.0765

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.110

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.121 AC: 18487 AN: 152194 Hom.: 1443 Cov.: 32 AF XY: 0.123 AC XY: 9142 AN XY: 74434

African (AFR) AF: 0.0787 AC: 3269 AN: 41526

American (AMR) AF: 0.260 AC: 3974 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0862 AC: 299 AN: 3470

East Asian (EAS) AF: 0.244 AC: 1260 AN: 5164

South Asian (SAS) AF: 0.0762 AC: 368 AN: 4830

European-Finnish (FIN) AF: 0.116 AC: 1235 AN: 10604

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.114 AC: 7717 AN: 67982

Other (OTH) AF: 0.109 AC: 230 AN: 2116

Alfa AF: 0.112 Hom.: 2290

Bravo AF: 0.135

Asia WGS AF: 0.153 AC: 530 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.14
CADD	Benign	15
DANN	Benign	0.90
PhyloP100		0.54
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: rs12596210; hg19: chr16-54027971;