chr17-74863166-G-T

Variant names:

• chr17-74863166-G-T
• rs1313895172
• NM_024417.5:c.1255C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024417.5(FDXR):​c.1255C>A​(p.Gln419Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 34)
• Consequence: FDXR NM_024417.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.29
• Publications: 1 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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17921925).

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.1255C>A	p.Gln419Lys	missense	Exon 11 of 12	NP_077728.3	A0A0C4DFN8
	FDXR	NM_001258012.4		c.1384C>A	p.Gln462Lys	missense	Exon 11 of 12	NP_001244941.2	A0A0A0MT64
	FDXR	NM_001258013.4		c.1348C>A	p.Gln450Lys	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.1255C>A	p.Gln419Lys	missense	Exon 11 of 12	ENSP00000293195.5	A0A0C4DFN8
	FDXR	ENST00000581530.5	TSL:1	c.1273C>A	p.Gln425Lys	missense	Exon 11 of 12	ENSP00000462972.1	A0A0C4DGN7
	FDXR	ENST00000578473.5	TSL:1	n.1943C>A		non_coding_transcript_exon	Exon 11 of 12

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD2 exomes AF: 0.00000400 AC: 1 AN: 249934 AF XY: 0.00000738

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000886

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
PhyloP100		6.3
gMVP		0.69

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

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

Other links and lift over

dbSNP: rs1313895172; hg19: chr17-72859288;