17-74863110-GCC-ACT

Variant names:

• chr17-74863110-GCC-ACT
• NM_024417.5:c.1309_1311delGGCinsAGT
• FDXR p.Gly437Ser

Variant summary

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

The NM_024417.5(FDXR):​c.1309_1311delGGCinsAGT​(p.Gly437Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: FDXR NM_024417.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.54
• Publications: 0 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 0 ACMG points.

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.1309_1311delGGCinsAGT	p.Gly437Ser	missense	N/A	NP_077728.3	A0A0C4DFN8
	FDXR	NM_001258012.4		c.1438_1440delGGCinsAGT	p.Gly480Ser	missense	N/A	NP_001244941.2	A0A0A0MT64
	FDXR	NM_001258013.4		c.1402_1404delGGCinsAGT	p.Gly468Ser	missense	N/A	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.1309_1311delGGCinsAGT	p.Gly437Ser	missense	N/A	ENSP00000293195.5	A0A0C4DFN8
	FDXR	ENST00000581530.5	TSL:1	c.1327_1329delGGCinsAGT	p.Gly443Ser	missense	N/A	ENSP00000462972.1	A0A0C4DGN7
	FDXR	ENST00000578473.5	TSL:1	n.1997_1999delGGCinsAGT		non_coding_transcript_exon	Exon 11 of 12

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.5

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr17-72859232;