NM_001397406.1:c.441G>T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The NM_001397406.1(FDX2):​c.441G>T​(p.Ser147Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000868 in 1,613,030 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign 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. S147S) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

FDX2
NM_001397406.1 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.457
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.57).
BP7
Synonymous conserved (PhyloP=-0.457 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FDX2NM_001397406.1 linkc.441G>T p.Ser147Ser synonymous_variant Exon 5 of 5 ENST00000393708.3 NP_001384335.1
FDX2-ZGLP1NR_176051.1 linkn.460G>T non_coding_transcript_exon_variant Exon 5 of 8
FDX2-ZGLP1NR_176052.1 linkn.521G>T 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.441G>T p.Ser147Ser synonymous_variant Exon 5 of 5 1 NM_001397406.1 ENSP00000377311.5 Q6P4F2
ENSG00000167807ENST00000452032.6 linkn.404G>T non_coding_transcript_exon_variant Exon 5 of 11 2 ENSP00000408510.3 E7EQL1

Frequencies

GnomAD3 genomes
AF:
0.00000661
AC:
1
AN:
151276
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251058
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135840
show subpopulations
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 SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000882
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000889
AC:
13
AN:
1461754
Hom.:
0
Cov.:
32
AF XY:
0.00000963
AC XY:
7
AN XY:
727180
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000117
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000661
AC:
1
AN:
151276
Hom.:
0
Cov.:
31
AF XY:
0.0000135
AC XY:
1
AN XY:
73842
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.57
CADD
Benign
0.61
DANN
Benign
0.88

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs149654332; hg19: chr19-10421273; API