Variant chr17-74863169-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBS1_SupportingBS2

The ENST00000293195.10(FDXR):c.1252G>A(p.Gly418Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000424 in 1,613,858 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00052 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00041 ( 5 hom. )

Consequence

FDXR
ENST00000293195.10 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.00

Variant links:

Genes affected

FDXR (HGNC:3642): (ferredoxin reductase) This gene encodes a mitochondrial flavoprotein that initiates electron transport for cytochromes P450 receiving electrons from NADPH. Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Apr 2012]

FDXR links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006870359).

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000519 (79/152358) while in subpopulation EAS AF= 0.00366 (19/5190). AF 95% confidence interval is 0.0024. There are 0 homozygotes in gnomad4. There are 45 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

BS2

High Homozygotes in GnomAdExome4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FDXR	NM_024417.5 linkuse as main transcript	c.1252G>A	p.Gly418Ser	missense_variant	11/12	ENST00000293195.10	NP_077728.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FDXR	ENST00000293195.10 linkuse as main transcript	c.1252G>A	p.Gly418Ser	missense_variant	11/12	1	NM_024417.5	ENSP00000293195	P3

Frequencies

GnomAD3 genomes

AF:

0.000525

AC:

AN:

152240

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.0118

Gnomad EAS

AF:

0.00365

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.000880

AC:

220

AN:

249898

Hom.:

AF XY:

0.000901

AC XY:

122

AN XY:

135416

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000580

Gnomad ASJ exome

AF:

0.0125

Gnomad EAS exome

AF:

0.00207

Gnomad SAS exome

AF:

0.000360

Gnomad FIN exome

AF:

0.0000468

Gnomad NFE exome

AF:

0.000310

Gnomad OTH exome

AF:

0.00131

GnomAD4 exome

AF:

0.000414

AC:

605

AN:

1461500

Hom.:

Cov.:

AF XY:

0.000443

AC XY:

322

AN XY:

727042

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000895

Gnomad4 ASJ exome

AF:

0.0105

Gnomad4 EAS exome

AF:

0.00194

Gnomad4 SAS exome

AF:

0.000464

Gnomad4 FIN exome

AF:

0.0000376

Gnomad4 NFE exome

AF:

0.000129

Gnomad4 OTH exome

AF:

0.00106

GnomAD4 genome

AF:

0.000519

AC:

AN:

152358

Hom.:

Cov.:

AF XY:

0.000604

AC XY:

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.0000240

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.0118

Gnomad4 EAS

AF:

0.00366

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000936

Hom.:

Bravo

AF:

0.000484

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000814

AC:

ExAC

AF:

0.000774

AC:

Asia WGS

AF:

0.00462

AC:

AN:

3478

EpiCase

AF:

0.000327

EpiControl

AF:

0.000178

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Mendelics

May 04, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.039

.;.;.;.;T;.;T;T

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.42

FATHMM_MKL

Uncertain

0.77

LIST_S2

Uncertain

0.90

D;D;D;D;D;D;D;D

M_CAP

Benign

0.025

MetaRNN

Benign

0.0069

T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

D;N;N;N;N;N;N;N;N

PrimateAI

Benign

0.32

PROVEAN

Uncertain

-2.8

.;D;D;.;.;D;.;D

REVEL

Benign

0.075

Sift

Benign

0.081

.;T;T;.;.;T;.;T

Sift4G

Benign

0.10

T;T;T;T;T;T;T;T

Vest4

0.16

MVP

0.33

MPC

0.25

ClinPred

0.044

GERP RS

2.6

gMVP

0.82

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.14

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