19-10310597-C-T

Variant names:

• chr19-10310597-C-T
• rs149654332
• NM_001397406.1:c.441G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Moderate BP6_Very_Strong BS2

The NM_001397406.1(FDX2):​c.441G>A​(p.Ser147Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0037 in 1,613,140 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0025 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0038 (10 hom.)
• Consequence: FDX2 NM_001397406.1 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.457
• Publications: 1 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.096).
• BP6: Variant 19-10310597-C-T is Benign according to our data. Variant chr19-10310597-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 384778.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAdExome4 at 10 AR gene

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.441G>A	p.Ser147Ser	synonymous	Exon 5 of 5	NP_001384335.1	Q6P4F2-1
	FDX2-ZGLP1	NR_176051.1		n.460G>A		non_coding_transcript_exon	Exon 5 of 8
	FDX2-ZGLP1	NR_176052.1		n.521G>A		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.441G>A	p.Ser147Ser	synonymous	Exon 5 of 5	ENSP00000377311.5	Q6P4F2-1
	ENSG00000167807	ENST00000452032.6	TSL:2	n.404G>A		non_coding_transcript_exon	Exon 5 of 11	ENSP00000408510.3	E7EQL1
	FDX2	ENST00000492239.5	TSL:2	c.36G>A	p.Ser12Ser	synonymous	Exon 4 of 4	ENSP00000488228.1	A0A0A0MTS8

Frequencies

GnomAD3 genomes AF: 0.00246 AC: 372 AN: 151276 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000755

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000992

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00187

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00461

Gnomad OTH AF: 0.00192

GnomAD2 exomes AF: 0.00239 AC: 599 AN: 251058 AF XY: 0.00261

Gnomad AFR exome AF: 0.000493

Gnomad AMR exome AF: 0.000925

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000462

Gnomad NFE exome AF: 0.00390

Gnomad OTH exome AF: 0.00245

GnomAD4 exome AF: 0.00383 AC: 5592 AN: 1461752 Hom.: 10 Cov.: 32 AF XY: 0.00371 AC XY: 2696 AN XY: 727180

African (AFR) AF: 0.000568 AC: 19 AN: 33478

American (AMR) AF: 0.00103 AC: 46 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00291 AC: 251 AN: 86258

European-Finnish (FIN) AF: 0.000581 AC: 31 AN: 53400

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00453 AC: 5037 AN: 1111920

Other (OTH) AF: 0.00343 AC: 207 AN: 60386

GnomAD4 genome AF: 0.00246 AC: 372 AN: 151388 Hom.: 0 Cov.: 31 AF XY: 0.00223 AC XY: 165 AN XY: 73962

African (AFR) AF: 0.000753 AC: 31 AN: 41190

American (AMR) AF: 0.000991 AC: 15 AN: 15142

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5128

South Asian (SAS) AF: 0.00187 AC: 9 AN: 4802

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10450

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00461 AC: 313 AN: 67894

Other (OTH) AF: 0.00190 AC: 4 AN: 2108

Alfa AF: 0.00242 Hom.: 0

Bravo AF: 0.00256

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.00376

EpiControl AF: 0.00456

ClinVar

ClinVar submissions

Significance: Benign/Likely 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
AlphaMissense	Benign	0.18
BayesDel_noAF	Benign	-0.63
CADD	Benign	6.5
DANN	Benign	0.86
PhyloP100		-0.46
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs149654332; hg19: chr19-10421273;