chr17-74863213-G-A
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM2PP3_StrongPP5_Moderate
The NM_024417.5(FDXR):c.1208C>T(p.Pro403Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,142 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Genomes: not found (cov: 34)
Exomes 𝑓: 0.0000048 ( 0 hom. )
Consequence
FDXR
NM_024417.5 missense
NM_024417.5 missense
Scores
6
6
3
Clinical Significance
Conservation
PhyloP100: 9.45
Genes affected
FDXR (HGNC:3642): (ferredoxin reductase) This gene encodes a mitochondrial flavoprotein that initiates electron transport for cytochromes P450 receiving electrons from NADPH. Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Apr 2012]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.942
PP5
?
Variant 17-74863213-G-A is Pathogenic according to our data. Variant chr17-74863213-G-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 1217114.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FDXR | NM_024417.5 | c.1208C>T | p.Pro403Leu | missense_variant | 11/12 | ENST00000293195.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FDXR | ENST00000293195.10 | c.1208C>T | p.Pro403Leu | missense_variant | 11/12 | 1 | NM_024417.5 | P3 |
Frequencies
GnomAD3 genomes ? Cov.: 34
GnomAD3 genomes
?
Cov.:
34
GnomAD3 exomes AF: 0.0000121 AC: 3AN: 248366Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 134778
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GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461142Hom.: 0 Cov.: 35 AF XY: 0.00000550 AC XY: 4AN XY: 726840
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GnomAD4 genome ? Cov.: 34
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ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Oct 09, 2020 | Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 29040572, 29554255) - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D;D;D;D;D;D;D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D;D;D;D;D;D
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D;D;D;D;D;D
PrimateAI
Uncertain
T
REVEL
Uncertain
Sift4G
Pathogenic
D;D;D;D;D;D;D;D
Vest4
MutPred
Loss of methylation at K400 (P = 0.0879);.;.;.;.;.;.;.;
MVP
MPC
0.88
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at