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GeneBe

17-74863963-T-A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 2P and 11B. PM2BP4_StrongBP6_ModerateBP7BS1

The NM_024417.5(FDXR):c.1107A>T(p.Pro369=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000456 in 1,614,036 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0024 ( 1 hom., cov: 33)
Exomes 𝑓: 0.00025 ( 0 hom. )

Consequence

FDXR
NM_024417.5 synonymous

Scores

1
1

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.408
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

PM2
?
    PM2 - Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
Very rare variant in population databases, with high coverage;
BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.67).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 17-74863963-T-A is Benign according to our data. Variant chr17-74863963-T-A is described in ClinVar as [Benign]. Clinvar id is 3039922.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.408 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00243 (370/152248) while in subpopulation AFR AF= 0.00864 (359/41554). AF 95% confidence interval is 0.0079. There are 1 homozygotes in gnomad4. There are 158 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
FDXRNM_024417.5 linkuse as main transcriptc.1107A>T p.Pro369= synonymous_variant 10/12 ENST00000293195.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
FDXRENST00000293195.10 linkuse as main transcriptc.1107A>T p.Pro369= synonymous_variant 10/121 NM_024417.5 P3

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00242
AC:
368
AN:
152130
Hom.:
1
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00862
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000458
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:
0.0000441
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.000724
AC:
182
AN:
251318
Hom.:
1
AF XY:
0.000530
AC XY:
72
AN XY:
135850
show subpopulations
Gnomad AFR exome
AF:
0.0102
Gnomad AMR exome
AF:
0.000289
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:
0.0000176
Gnomad OTH exome
AF:
0.000653
GnomAD4 exome
AF:
0.000250
AC:
366
AN:
1461788
Hom.:
0
Cov.:
32
AF XY:
0.000201
AC XY:
146
AN XY:
727196
show subpopulations
Gnomad4 AFR exome
AF:
0.00947
Gnomad4 AMR exome
AF:
0.000358
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:
0.00000360
Gnomad4 OTH exome
AF:
0.000480
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00243
AC:
370
AN:
152248
Hom.:
1
Cov.:
33
AF XY:
0.00212
AC XY:
158
AN XY:
74440
show subpopulations
Gnomad4 AFR
AF:
0.00864
Gnomad4 AMR
AF:
0.000457
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.000603
Hom.:
0
Bravo
AF:
0.00290
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

FDXR-related disorder Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesMar 31, 2021This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.67
Cadd
Benign
8.3
Dann
Uncertain
0.98
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.070
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: rs143268395; hg19: chr17-72860085; API