chr16-53888926-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001080432.3(FTO):​c.1214C>T​(p.Ala405Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00164 in 1,614,068 control chromosomes in the GnomAD database, including 39 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0087 ( 24 hom., cov: 32)
Exomes 𝑓: 0.00091 ( 15 hom. )

Consequence

FTO
NM_001080432.3 missense

Scores

1
17

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.639
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0025675297).
BP6
Variant 16-53888926-C-T is Benign according to our data. Variant chr16-53888926-C-T is described in ClinVar as [Benign]. Clinvar id is 784339.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00872 (1328/152312) while in subpopulation AFR AF= 0.0305 (1266/41568). AF 95% confidence interval is 0.0291. There are 24 homozygotes in gnomad4. There are 620 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 24 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
FTONM_001080432.3 linkuse as main transcriptc.1214C>T p.Ala405Val missense_variant 7/9 ENST00000471389.6 NP_001073901.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
FTOENST00000471389.6 linkuse as main transcriptc.1214C>T p.Ala405Val missense_variant 7/91 NM_001080432.3 ENSP00000418823 P1Q9C0B1-1

Frequencies

GnomAD3 genomes
AF:
0.00868
AC:
1321
AN:
152194
Hom.:
23
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0304
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00268
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000588
Gnomad OTH
AF:
0.00765
GnomAD3 exomes
AF:
0.00208
AC:
523
AN:
251442
Hom.:
14
AF XY:
0.00145
AC XY:
197
AN XY:
135892
show subpopulations
Gnomad AFR exome
AF:
0.0290
Gnomad AMR exome
AF:
0.00101
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000879
Gnomad OTH exome
AF:
0.000814
GnomAD4 exome
AF:
0.000907
AC:
1326
AN:
1461756
Hom.:
15
Cov.:
32
AF XY:
0.000781
AC XY:
568
AN XY:
727198
show subpopulations
Gnomad4 AFR exome
AF:
0.0318
Gnomad4 AMR exome
AF:
0.00107
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000580
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000657
Gnomad4 OTH exome
AF:
0.00204
GnomAD4 genome
AF:
0.00872
AC:
1328
AN:
152312
Hom.:
24
Cov.:
32
AF XY:
0.00833
AC XY:
620
AN XY:
74470
show subpopulations
Gnomad4 AFR
AF:
0.0305
Gnomad4 AMR
AF:
0.00268
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.00757
Alfa
AF:
0.00195
Hom.:
9
Bravo
AF:
0.00958
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000519
AC:
2
ESP6500AA
AF:
0.0282
AC:
124
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.00258
AC:
313
Asia WGS
AF:
0.00173
AC:
6
AN:
3478
EpiCase
AF:
0.000109
EpiControl
AF:
0.000178

ClinVar

Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 17, 2024- -
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Lethal polymalformative syndrome, Boissel type Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaApr 27, 2017This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.080
BayesDel_addAF
Benign
-0.62
T
BayesDel_noAF
Benign
-0.65
CADD
Benign
9.2
DANN
Benign
0.94
DEOGEN2
Benign
0.026
T;.;T;T;.;T;.;.
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.28
N
LIST_S2
Uncertain
0.95
D;D;D;D;D;D;.;D
MetaRNN
Benign
0.0026
T;T;T;T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.0
.;.;N;.;.;.;.;.
MutationTaster
Benign
1.0
N;N;N;N
PrimateAI
Benign
0.23
T
PROVEAN
Benign
-1.1
.;.;N;.;.;.;N;N
REVEL
Benign
0.030
Sift
Benign
0.14
.;.;T;.;.;.;T;T
Sift4G
Benign
0.20
.;.;T;.;.;.;T;T
Polyphen
0.025
.;.;B;.;.;.;.;.
Vest4
0.20, 0.15
MVP
0.088
MPC
0.20
ClinPred
0.0016
T
GERP RS
-3.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.082
gMVP
0.11

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: rs16952624; hg19: chr16-53922838; API