Variant 11-110430133-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_004109.5(FDX1):c.13G>A(p.Gly5Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0103 in 1,239,336 control chromosomes in the GnomAD database, including 70 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0076 ( 7 hom., cov: 32)

Exomes 𝑓: 0.011 ( 63 hom. )

Consequence

FDX1
NM_004109.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.428

Variant links:

Genes affected

FDX1 (HGNC:3638): (ferredoxin 1) This gene encodes a small iron-sulfur protein that transfers electrons from NADPH through ferredoxin reductase to mitochondrial cytochrome P450, involved in steroid, vitamin D, and bile acid metabolism. Pseudogenes of this functional gene are found on chromosomes 20 and 21. [provided by RefSeq, Aug 2011]

FDX1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0057221055).

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FDX1	NM_004109.5 linkuse as main transcript	c.13G>A	p.Gly5Arg	missense_variant	1/4	ENST00000260270.3	NP_004100.1
FDX1	XM_047426566.1 linkuse as main transcript	c.8+780G>A		intron_variant			XP_047282522.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FDX1	ENST00000260270.3 linkuse as main transcript	c.13G>A	p.Gly5Arg	missense_variant	1/4	1	NM_004109.5	ENSP00000260270	P1

Frequencies

GnomAD3 genomes

AF:

0.00765

AC:

1162

AN:

151858

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00227

Gnomad AMI

AF:

0.0253

Gnomad AMR

AF:

0.0104

Gnomad ASJ

AF:

0.00374

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.00904

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0111

Gnomad OTH

AF:

0.0100

GnomAD3 exomes

AF:

0.00725

AC:

AN:

1518

Hom.:

AF XY:

0.0103

AC XY:

AN XY:

872

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00694

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0115

Gnomad OTH exome

AF:

0.0200

GnomAD4 exome

AF:

0.0107

AC:

11659

AN:

1087370

Hom.:

Cov.:

AF XY:

0.0108

AC XY:

5618

AN XY:

519626

show subpopulations

Gnomad4 AFR exome

AF:

0.00156

Gnomad4 AMR exome

AF:

0.00755

Gnomad4 ASJ exome

AF:

0.00271

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000843

Gnomad4 FIN exome

AF:

0.00657

Gnomad4 NFE exome

AF:

0.0119

Gnomad4 OTH exome

AF:

0.00775

GnomAD4 genome

AF:

0.00765

AC:

1162

AN:

151966

Hom.:

Cov.:

AF XY:

0.00769

AC XY:

571

AN XY:

74298

show subpopulations

Gnomad4 AFR

AF:

0.00226

Gnomad4 AMR

AF:

0.0104

Gnomad4 ASJ

AF:

0.00374

Gnomad4 EAS

AF:

0.000195

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00904

Gnomad4 NFE

AF:

0.0111

Gnomad4 OTH

AF:

0.00993

Alfa

AF:

0.00369

Hom.:

Bravo

AF:

0.00727

ExAC

AF:

0.00101

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 10, 2021

The c.13G>A (p.G5R) alteration is located in exon 1 (coding exon 1) of the FDX1 gene. This alteration results from a G to A substitution at nucleotide position 13, causing the glycine (G) at amino acid position 5 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.30

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.18

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.097

Eigen

Benign

-0.75

Eigen_PC

Benign

-0.82

FATHMM_MKL

Benign

0.00063

LIST_S2

Benign

0.58

MetaRNN

Benign

0.0057

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.55

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-0.20

REVEL

Benign

0.051

Sift

Benign

0.10

Sift4G

Uncertain

0.023

Polyphen

0.46

Vest4

0.21

MutPred

0.31

Gain of methylation at A5 (P = 0.0024);

MVP

0.45

MPC

0.089

ClinPred

0.086

GERP RS

1.0

Varity_R

0.054

gMVP

0.40

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over