19-10310591-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 6P and 1B. PM2PP3_StrongBP7

The NM_001397406.1(FDX2):​c.447G>A​(p.Leu149Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L149L) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 31)

Consequence

FDX2
NM_001397406.1 synonymous

Scores

1
1

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.26
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 5 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
BayesDel_noAF computational evidence supports a deleterious effect, 0.56
BP7
Synonymous conserved (PhyloP=1.26 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FDX2NM_001397406.1 linkc.447G>A p.Leu149Leu synonymous_variant Exon 5 of 5 ENST00000393708.3 NP_001384335.1
FDX2-ZGLP1NR_176051.1 linkn.466G>A non_coding_transcript_exon_variant Exon 5 of 8
FDX2-ZGLP1NR_176052.1 linkn.527G>A non_coding_transcript_exon_variant Exon 5 of 9

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FDX2ENST00000393708.3 linkc.447G>A p.Leu149Leu synonymous_variant Exon 5 of 5 1 NM_001397406.1 ENSP00000377311.5 Q6P4F2
ENSG00000167807ENST00000452032.6 linkn.410G>A non_coding_transcript_exon_variant Exon 5 of 11 2 ENSP00000408510.3 E7EQL1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Pathogenic
0.56
CADD
Benign
6.2
DANN
Uncertain
0.98

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.070
Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-10421267; API