Variant 11-110430194-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004109.5(FDX1):c.74T>C(p.Leu25Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000489 in 1,227,200 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000037 ( 0 hom. )

Consequence

FDX1
NM_004109.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.42

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07349393).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FDX1	NM_004109.5 linkuse as main transcript	c.74T>C	p.Leu25Pro	missense_variant	1/4	ENST00000260270.3	NP_004100.1
FDX1	XM_047426566.1 linkuse as main transcript	c.8+841T>C		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.74T>C	p.Leu25Pro	missense_variant	1/4	1	NM_004109.5	ENSP00000260270	P1

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151556

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000295

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000372

AC:

AN:

1075644

Hom.:

Cov.:

AF XY:

0.00000391

AC XY:

AN XY:

511950

show subpopulations

Gnomad4 AFR exome

AF:

0.0000451

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000218

Gnomad4 OTH exome

AF:

0.0000235

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151556

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74022

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000295

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000189

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 14, 2024

The c.74T>C (p.L25P) alteration is located in exon 1 (coding exon 1) of the FDX1 gene. This alteration results from a T to C substitution at nucleotide position 74, causing the leucine (L) at amino acid position 25 to be replaced by a proline (P). 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

0.087

BayesDel_addAF

Benign

-0.086

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Benign

0.84

DEOGEN2

Benign

0.13

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.00027

LIST_S2

Benign

0.35

M_CAP

Benign

0.070

MetaRNN

Benign

0.073

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-1.1

REVEL

Benign

0.035

Sift

Benign

0.032

Sift4G

Uncertain

0.035

Polyphen

0.0010

Vest4

0.47

MutPred

0.26

Gain of loop (P = 0.0312);

MVP

0.26

MPC

0.14

ClinPred

0.23

GERP RS

-6.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.0

Varity_R

0.32

gMVP

0.54

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