16-53704202-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001080432.3(FTO):c.18T>C(p.Thr6Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00488 in 1,551,466 control chromosomes in the GnomAD database, including 311 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.026 ( 170 hom., cov: 32)

Exomes 𝑓: 0.0026 ( 141 hom. )

Consequence

FTO
NM_001080432.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.452

Publications

6 publications found

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]

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

FTO links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 16-53704202-T-C is Benign according to our data. Variant chr16-53704202-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 319677.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.452 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0875 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FTO	NM_001080432.3 link	c.18T>C	p.Thr6Thr	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
FTO	ENST00000471389.6 link	c.18T>C	p.Thr6Thr	synonymous_variant	Exon 1 of 9	1	NM_001080432.3	ENSP00000418823.1		Q9C0B1-1

Frequencies

GnomAD3 genomes

AF:

0.0259

AC:

3946

AN:

152174

Hom.:

170

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0901

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00916

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000470

Gnomad OTH

AF:

0.0177

GnomAD2 exomes

AF:

0.00593

AC:

916

AN:

154476

AF XY:

0.00428

show subpopulations

Gnomad AFR exome

AF:

0.0895

Gnomad AMR exome

AF:

0.00408

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000324

Gnomad OTH exome

AF:

0.00319

GnomAD4 exome

AF:

0.00259

AC:

3625

AN:

1399174

Hom.:

141

Cov.:

AF XY:

0.00227

AC XY:

1567

AN XY:

690120

show subpopulations

African (AFR)

AF:

0.0924

AC:

2919

AN:

31588

American (AMR)

AF:

0.00479

AC:

171

AN:

35696

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25178

East Asian (EAS)

AF:

0.00

AC:

AN:

35738

South Asian (SAS)

AF:

0.000265

AC:

AN:

79228

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49256

Middle Eastern (MID)

AF:

0.00387

AC:

AN:

5692

European-Non Finnish (NFE)

AF:

0.000138

AC:

149

AN:

1078814

Other (OTH)

AF:

0.00592

AC:

343

AN:

57984

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

208

417

625

834

1042

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0259

AC:

3947

AN:

152292

Hom.:

170

Cov.:

AF XY:

0.0249

AC XY:

1855

AN XY:

74470

show subpopulations

African (AFR)

AF:

0.0899

AC:

3735

AN:

41550

American (AMR)

AF:

0.00915

AC:

140

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.000207

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000470

AC:

AN:

68034

Other (OTH)

AF:

0.0175

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

173

347

520

694

867

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0216

Hom.:

102

Bravo

AF:

0.0292

Asia WGS

AF:

0.00520

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Lethal polymalformative syndrome, Boissel type

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Joubert syndrome

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nephronophthisis

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Meckel-Gruber syndrome

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

9.7

(source)

DANN

Benign

0.70

PhyloP100

-0.45

PromoterAI

0.0065

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=300/0

polymorphism (auto)

(source)

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

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16-53704202-T-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over