11-110430245-G-A

Variant summary

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

The NM_004109.5(FDX1):​c.125G>A​(p.Gly42Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)

Consequence

FDX1
NM_004109.5 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.541
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]

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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=0.14133242).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
FDX1NM_004109.5 linkuse as main transcriptc.125G>A p.Gly42Glu missense_variant 1/4 ENST00000260270.3 NP_004100.1
FDX1XM_047426566.1 linkuse as main transcriptc.8+892G>A intron_variant XP_047282522.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
FDX1ENST00000260270.3 linkuse as main transcriptc.125G>A p.Gly42Glu missense_variant 1/41 NM_004109.5 ENSP00000260270 P1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

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 submitterclinical testingAmbry GeneticsJan 09, 2024The c.125G>A (p.G42E) 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 125, causing the glycine (G) at amino acid position 42 to be replaced by a glutamic acid (E). 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
0.11
BayesDel_addAF
Benign
-0.090
T
BayesDel_noAF
Benign
-0.37
CADD
Benign
9.2
DANN
Benign
0.88
DEOGEN2
Benign
0.083
T
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.2
FATHMM_MKL
Benign
0.0010
N
LIST_S2
Benign
0.49
T
M_CAP
Benign
0.070
D
MetaRNN
Benign
0.14
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.81
L
MutationTaster
Benign
1.0
N
PrimateAI
Uncertain
0.73
T
PROVEAN
Benign
-0.41
N
REVEL
Benign
0.074
Sift
Benign
0.095
T
Sift4G
Benign
0.33
T
Polyphen
0.77
P
Vest4
0.14
MutPred
0.26
Loss of MoRF binding (P = 0.0379);
MVP
0.23
MPC
0.097
ClinPred
0.46
T
GERP RS
0.97
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0
Varity_R
0.032
gMVP
0.41

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-110300969; API