rs766147142

Variant names:

• chr17-74863112-C-T
• rs766147142
• NM_024417.5:c.1309G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-74863112-C-T
• chr17-74863112-C-A
• chr17-74863112-C-G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_024417.5(FDXR):​c.1309G>A​(p.Gly437Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 34)
• Consequence: FDXR NM_024417.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter P:1 U:1
• Conservation: PhyloP100: 5.51
• Publications: 6 publications found

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: Orphanet, Labcorp Genetics (formerly Invitae), G2P
• optic atrophy-ataxia-peripheral neuropathy-global developmental delay syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FDXR	NM_024417.5	MANE Select	c.1309G>A	p.Gly437Ser	missense	Exon 11 of 12	NP_077728.3	A0A0C4DFN8
	FDXR	NM_001258012.4		c.1438G>A	p.Gly480Ser	missense	Exon 11 of 12	NP_001244941.2	A0A0A0MT64
	FDXR	NM_001258013.4		c.1402G>A	p.Gly468Ser	missense	Exon 12 of 13	NP_001244942.2	A0A0A0MSZ4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FDXR	ENST00000293195.10	TSL:1 MANE Select	c.1309G>A	p.Gly437Ser	missense	Exon 11 of 12	ENSP00000293195.5	A0A0C4DFN8
	FDXR	ENST00000581530.5	TSL:1	c.1327G>A	p.Gly443Ser	missense	Exon 11 of 12	ENSP00000462972.1	A0A0C4DGN7
	FDXR	ENST00000578473.5	TSL:1	n.1997G>A		non_coding_transcript_exon	Exon 11 of 12

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 34

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
1	-	-	Auditory neuropathy-optic atrophy syndrome (1)
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.45
BayesDel_addAF	Uncertain	0.046	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.082	T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.080	D
MetaRNN	Uncertain	0.61	D
MetaSVM	Benign	-0.98	T
PhyloP100		5.5
PrimateAI	Benign	0.45	T
PROVEAN	Pathogenic	-4.9	D
REVEL	Benign	0.21
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.033	D
Vest4		0.64
MutPred		0.42		Loss of helix (P = 0.0123)
MVP		0.56
MPC		0.60
ClinPred		0.99	D
GERP RS		3.8
gMVP		0.87
Mutation Taster		=0/100	disease causing

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

Other links and lift over

dbSNP: rs766147142; hg19: chr17-72859234;