NM_001397406.1:c.498G>T

Variant names:

• chr19-10310540-C-A
• rs1048941
• NM_001397406.1:c.498G>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_001397406.1(FDX2):​c.498G>T​(p.Leu166Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00428 in 1,614,128 control chromosomes in the GnomAD database, including 253 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. L166L) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.023 (122 hom., cov: 31)
  • Exomes 𝑓: 0.0024 (131 hom.)
• Consequence: FDX2 NM_001397406.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.00100
• Publications: 2 publications found

Genes affected

FDX2 (HGNC:30546): (ferredoxin 2) This gene encodes a member of the ferredoxin family. The encoded protein contains a 2Fe-2S ferredoxin-type domain and is essential for heme A and Fe/S protein biosynthesis. Mutation in FDX1L gene is associated with mitochondrial muscle myopathy. [provided by RefSeq, Sep 2014]

FDX2 Gene-Disease associations (from GenCC):

• mitochondrial myopathy, episodic, with optic atrophy and reversible leukoencephalopathy

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ENSG00000167807 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BP6: Variant 19-10310540-C-A is Benign according to our data. Variant chr19-10310540-C-A is described in ClinVar as Benign. ClinVar VariationId is 383056.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.001 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0769 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001397406.1. 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
	FDX2	NM_001397406.1	MANE Select	c.498G>T	p.Leu166Leu	synonymous	Exon 5 of 5	NP_001384335.1	Q6P4F2-1
	FDX2-ZGLP1	NR_176051.1		n.517G>T		non_coding_transcript_exon	Exon 5 of 8
	FDX2-ZGLP1	NR_176052.1		n.578G>T		non_coding_transcript_exon	Exon 5 of 9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FDX2	ENST00000393708.3	TSL:1 MANE Select	c.498G>T	p.Leu166Leu	synonymous	Exon 5 of 5	ENSP00000377311.5	Q6P4F2-1
	ENSG00000167807	ENST00000452032.6	TSL:2	n.*32G>T		non_coding_transcript_exon	Exon 5 of 11	ENSP00000408510.3	E7EQL1
	ENSG00000167807	ENST00000452032.6	TSL:2	n.*32G>T		3_prime_UTR	Exon 5 of 11	ENSP00000408510.3	E7EQL1

Frequencies

GnomAD3 genomes AF: 0.0227 AC: 3456 AN: 152132 Hom.: 123 Cov.: 31

Gnomad AFR AF: 0.0793

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00806

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000279

Gnomad OTH AF: 0.0129

GnomAD2 exomes AF: 0.00589 AC: 1480 AN: 251064 AF XY: 0.00439

Gnomad AFR exome AF: 0.0817

Gnomad AMR exome AF: 0.00338

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000176

Gnomad OTH exome AF: 0.00245

GnomAD4 exome AF: 0.00235 AC: 3440 AN: 1461878 Hom.: 131 Cov.: 32 AF XY: 0.00194 AC XY: 1412 AN XY: 727242

African (AFR) AF: 0.0835 AC: 2794 AN: 33480

American (AMR) AF: 0.00416 AC: 186 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000812 AC: 7 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00173 AC: 10 AN: 5768

European-Non Finnish (NFE) AF: 0.000156 AC: 173 AN: 1112008

Other (OTH) AF: 0.00447 AC: 270 AN: 60394

GnomAD4 genome AF: 0.0227 AC: 3461 AN: 152250 Hom.: 122 Cov.: 31 AF XY: 0.0222 AC XY: 1649 AN XY: 74430

African (AFR) AF: 0.0792 AC: 3288 AN: 41532

American (AMR) AF: 0.00805 AC: 123 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000279 AC: 19 AN: 68020

Other (OTH) AF: 0.0128 AC: 27 AN: 2112

Alfa AF: 0.0139 Hom.: 41

Bravo AF: 0.0260

Asia WGS AF: 0.00260 AC: 9 AN: 3478

EpiCase AF: 0.000327

EpiControl AF: 0.000296

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	7.7
DANN	Benign	0.87
PhyloP100		-0.0010
Mutation Taster		=90/10	polymorphism (auto)

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: rs1048941; hg19: chr19-10421216;