11-110430182-C-G

Variant summary

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

The NM_004109.5(FDX1):ā€‹c.62C>Gā€‹(p.Ala21Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,231,754 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 32)
Exomes š‘“: 0.000014 ( 0 hom. )

Consequence

FDX1
NM_004109.5 missense

Scores

1
1
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.468
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]

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=0.081455916).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
FDX1NM_004109.5 linkuse as main transcriptc.62C>G p.Ala21Gly missense_variant 1/4 ENST00000260270.3 NP_004100.1
FDX1XM_047426566.1 linkuse as main transcriptc.8+829C>G intron_variant XP_047282522.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
FDX1ENST00000260270.3 linkuse as main transcriptc.62C>G p.Ala21Gly missense_variant 1/41 NM_004109.5 ENSP00000260270 P1

Frequencies

GnomAD3 genomes
AF:
0.00000659
AC:
1
AN:
151692
Hom.:
0
Cov.:
32
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.0000139
AC:
15
AN:
1080062
Hom.:
0
Cov.:
30
AF XY:
0.0000136
AC XY:
7
AN XY:
514738
show subpopulations
Gnomad4 AFR exome
AF:
0.00
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:
0.0000141
Gnomad4 OTH exome
AF:
0.0000234
GnomAD4 genome
AF:
0.00000659
AC:
1
AN:
151692
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74072
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:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378

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 GeneticsDec 16, 2021The c.62C>G (p.A21G) alteration is located in exon 1 (coding exon 1) of the FDX1 gene. This alteration results from a C to G substitution at nucleotide position 62, causing the alanine (A) at amino acid position 21 to be replaced by a glycine (G). 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
0.065
BayesDel_addAF
Benign
-0.084
T
BayesDel_noAF
Benign
-0.36
CADD
Benign
7.3
DANN
Uncertain
0.98
DEOGEN2
Benign
0.10
T
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.00018
N
LIST_S2
Benign
0.29
T
M_CAP
Benign
0.054
D
MetaRNN
Benign
0.081
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.55
N
MutationTaster
Benign
1.0
N
PrimateAI
Pathogenic
0.79
T
PROVEAN
Benign
-0.72
N
REVEL
Benign
0.020
Sift
Benign
0.33
T
Sift4G
Benign
0.24
T
Polyphen
0.092
B
Vest4
0.12
MutPred
0.29
Gain of relative solvent accessibility (P = 0.0082);
MVP
0.14
MPC
0.081
ClinPred
0.33
T
GERP RS
1.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0
Varity_R
0.040
gMVP
0.39

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: rs1215034393; hg19: chr11-110300906; API