rs1464247091

Variant names:

• chr19-10310499-G-A
• NM_001397406.1:c.539C>T

Your query was ambiguous. Multiple possible variants found:

• chr19-10310499-G-A
• chr19-10310499-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001397406.1(FDX2):​c.539C>T​(p.Pro180Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P180R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: FDX2 NM_001397406.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.79

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]

ENSG00000167807 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.832

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FDX2	NM_001397406.1	c.539C>T	p.Pro180Leu	missense_variant	Exon 5 of 5	ENST00000393708.3	NP_001384335.1
FDX2-ZGLP1	NR_176051.1	n.558C>T		non_coding_transcript_exon_variant	Exon 5 of 8
FDX2-ZGLP1	NR_176052.1	n.619C>T		non_coding_transcript_exon_variant	Exon 5 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FDX2	ENST00000393708.3	c.539C>T	p.Pro180Leu	missense_variant	Exon 5 of 5	1	NM_001397406.1	ENSP00000377311.5
ENSG00000167807	ENST00000452032.6	n.*73C>T		non_coding_transcript_exon_variant	Exon 5 of 11	2		ENSP00000408510.3
ENSG00000167807	ENST00000452032.6	n.*73C>T		3_prime_UTR_variant	Exon 5 of 11	2		ENSP00000408510.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461874 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727238

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.82
BayesDel_addAF	Pathogenic	0.32	D
BayesDel_noAF	Pathogenic	0.22
CADD	Pathogenic	28
DANN	Uncertain	1.0
Eigen	Pathogenic	0.84
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Pathogenic	1.0	D;.;D
M_CAP	Uncertain	0.17	D
MetaRNN	Pathogenic	0.83	D;D;D
MetaSVM	Uncertain	0.37	D
PrimateAI	Uncertain	0.61	T
REVEL	Uncertain	0.59
Sift4G	Pathogenic	0.0	D;D;D
Vest4		0.82
MVP		0.65
MPC		1.2
ClinPred		1.0	D
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.40
gMVP		0.76

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-10421175;