Genetic Variant FDXR:p.Phe51Leu (chr17-74872062-A-G) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_024417.5(FDXR):c.151T>C(p.Phe51Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

FDXR
NM_024417.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.45

Publications

4 publications found

Variant links:

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]

FDXR Gene-Disease associations (from GenCC):

auditory neuropathy-optic atrophy syndrome
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: PanelApp Australia, Orphanet, G2P, Labcorp Genetics (formerly Invitae)
optic atrophy-ataxia-peripheral neuropathy-global developmental delay syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

FDXR links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.809

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024417.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
FDXR	NM_024417.5	MANE Select	c.151T>C	p.Phe51Leu	missense	Exon 2 of 12	NP_077728.3
FDXR	NM_001258012.4		c.151T>C	p.Phe51Leu	missense	Exon 2 of 12	NP_001244941.2
FDXR	NM_001258013.4		c.244T>C	p.Phe82Leu	missense	Exon 3 of 13	NP_001244942.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
FDXR	ENST00000293195.10	TSL:1 MANE Select	c.151T>C	p.Phe51Leu	missense	Exon 2 of 12	ENSP00000293195.5
FDXR	ENST00000581530.5	TSL:1	c.151T>C	p.Phe51Leu	missense	Exon 2 of 12	ENSP00000462972.1
FDXR	ENST00000578473.5	TSL:1	n.836T>C		non_coding_transcript_exon	Exon 2 of 12

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1450686

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

721218

African (AFR)

AF:

0.00

AC:

AN:

32984

American (AMR)

AF:

0.00

AC:

AN:

43004

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25366

East Asian (EAS)

AF:

0.00

AC:

AN:

39608

South Asian (SAS)

AF:

0.00

AC:

AN:

84668

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53082

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5656

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1106416

Other (OTH)

AF:

0.00

AC:

AN:

59902

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

May 26, 2016

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.99

BayesDel_addAF

Uncertain

0.15

BayesDel_noAF

Uncertain

-0.030

CADD

Uncertain

(source)

DANN

Benign

0.83

DEOGEN2

Benign

0.068

Eigen

Uncertain

0.19

Eigen_PC

Benign

0.21

FATHMM_MKL

Uncertain

0.97

LIST_S2

Pathogenic

0.99

M_CAP

Uncertain

0.19

MetaRNN

Pathogenic

0.81

MetaSVM

Uncertain

-0.28

MutationAssessor

Benign

0.015

PhyloP100

8.4

PrimateAI

Uncertain

0.74

PROVEAN

Pathogenic

-5.1

REVEL

Uncertain

0.58

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.0060

Vest4

0.76

MutPred

0.63

Gain of phosphorylation at T53 (P = 0.1974)

MVP

0.93

MPC

0.62

ClinPred

0.99

GERP RS

4.3

gMVP

0.43

Mutation Taster

=0/100

disease causing

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over