Variant 11-110456995-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_004109.5(FDX1):c.388A>G(p.Ile130Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000922 in 1,613,796 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00065 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00095 ( 0 hom. )

Consequence

FDX1
NM_004109.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.37

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.013612509).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FDX1	NM_004109.5 linkuse as main transcript	c.388A>G	p.Ile130Val	missense_variant	3/4	ENST00000260270.3	NP_004100.1
FDX1	XM_047426566.1 linkuse as main transcript	c.211A>G	p.Ile71Val	missense_variant	3/4		XP_047282522.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FDX1	ENST00000260270.3 linkuse as main transcript	c.388A>G	p.Ile130Val	missense_variant	3/4	1	NM_004109.5	ENSP00000260270	P1

Frequencies

GnomAD3 genomes

AF:

0.000650

AC:

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00126

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000557

AC:

140

AN:

251232

Hom.:

AF XY:

0.000589

AC XY:

AN XY:

135778

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.000319

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.00103

Gnomad OTH exome

AF:

0.000490

GnomAD4 exome

AF:

0.000950

AC:

1389

AN:

1461482

Hom.:

Cov.:

AF XY:

0.000919

AC XY:

668

AN XY:

727006

show subpopulations

Gnomad4 AFR exome

AF:

0.000269

Gnomad4 AMR exome

AF:

0.000492

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000928

Gnomad4 FIN exome

AF:

0.000112

Gnomad4 NFE exome

AF:

0.00117

Gnomad4 OTH exome

AF:

0.000778

GnomAD4 genome

AF:

0.000650

AC:

AN:

152314

Hom.:

Cov.:

AF XY:

0.000604

AC XY:

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.000192

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.00126

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000939

Hom.:

Bravo

AF:

0.000718

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.000814

AC:

ExAC

AF:

0.000519

AC:

EpiCase

AF:

0.000765

EpiControl

AF:

0.00136

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

May 27, 2022

The c.388A>G (p.I130V) alteration is located in exon 3 (coding exon 3) of the FDX1 gene. This alteration results from a A to G substitution at nucleotide position 388, causing the isoleucine (I) at amino acid position 130 to be replaced by a valine (V). 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

0.068

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.44

DEOGEN2

Benign

0.13

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.44

FATHMM_MKL

Benign

0.68

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.0036

MetaRNN

Benign

0.014

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

MutationTaster

Benign

0.98

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.28

REVEL

Benign

0.036

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0050

Vest4

0.36

MVP

0.34

MPC

0.067

ClinPred

0.012

GERP RS

3.1

Varity_R

0.13

gMVP

0.55

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