Variant 19-10310597-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001397406.1(FDX2):c.441G>A(p.Ser147=) 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

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

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]

FDX2 links:

FDX2-ZGLP1 (HGNC:):

FDX2-ZGLP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BP6

Variant 19-10310597-C-T is Benign according to our data. Variant chr19-10310597-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 384778.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
FDX2	NM_001397406.1 linkuse as main transcript	c.441G>A	p.Ser147=	synonymous_variant	5/5	ENST00000393708.3	NP_001384335.1
FDX2-ZGLP1	NR_176051.1 linkuse as main transcript	n.460G>A		non_coding_transcript_exon_variant	5/8
FDX2-ZGLP1	NR_176052.1 linkuse as main transcript	n.521G>A		non_coding_transcript_exon_variant	5/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FDX2	ENST00000393708.3 linkuse as main transcript	c.441G>A	p.Ser147=	synonymous_variant	5/5	1	NM_001397406.1	ENSP00000377311	P1

Frequencies

GnomAD3 genomes

AF:

0.00246

AC:

372

AN:

151276

Hom.:

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.00239

AC:

599

AN:

251058

Hom.:

AF XY:

0.00261

AC XY:

354

AN XY:

135840

show subpopulations

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 SAS exome

AF:

0.00301

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.:

Cov.:

AF XY:

0.00371

AC XY:

2696

AN XY:

727180

show subpopulations

Gnomad4 AFR exome

AF:

0.000568

Gnomad4 AMR exome

AF:

0.00103

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00291

Gnomad4 FIN exome

AF:

0.000581

Gnomad4 NFE exome

AF:

0.00453

Gnomad4 OTH exome

AF:

0.00343

GnomAD4 genome

AF:

0.00246

AC:

372

AN:

151388

Hom.:

Cov.:

AF XY:

0.00223

AC XY:

165

AN XY:

73962

show subpopulations

Gnomad4 AFR

AF:

0.000753

Gnomad4 AMR

AF:

0.000991

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00187

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00461

Gnomad4 OTH

AF:

0.00190

Alfa

AF:

0.00273

Hom.:

Bravo

AF:

0.00256

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.00376

EpiControl

AF:

0.00456

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 26, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jan 01, 2024	FDX2: BP4, BP7 -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 12, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

6.5

DANN

Benign

0.86

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over