Variant 22-36490244-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001102371.2(FOXRED2):c.1819A>G(p.Thr607Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000343 in 1,459,026 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

FOXRED2
NM_001102371.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.73

Variant links:

Genes affected

FOXRED2 (HGNC:26264): (FAD dependent oxidoreductase domain containing 2) Enables flavin adenine dinucleotide binding activity. Involved in ubiquitin-dependent ERAD pathway. Located in endoplasmic reticulum lumen. [provided by Alliance of Genome Resources, Apr 2022]

FOXRED2 links:

FOXRED2 (HGNC:):

FOXRED2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.25616154).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOXRED2	NM_001102371.2 linkuse as main transcript	c.1819A>G	p.Thr607Ala	missense_variant	9/9	ENST00000397224.9	NP_001095841.1	Q8IWF2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOXRED2	ENST00000397224.9 linkuse as main transcript	c.1819A>G	p.Thr607Ala	missense_variant	9/9	1	NM_001102371.2	ENSP00000380401.4		Q8IWF2-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000808

AC:

AN:

247434

Hom.:

AF XY:

0.00000746

AC XY:

AN XY:

133984

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000292

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:

0.00

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.00000343

AC:

AN:

1459026

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

725496

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000674

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:

9.01e-7

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

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

Ambry Genetics

Jan 08, 2024

The c.1819A>G (p.T607A) alteration is located in exon 9 (coding exon 8) of the FOXRED2 gene. This alteration results from a A to G substitution at nucleotide position 1819, causing the threonine (T) at amino acid position 607 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.013

T;T;T

Eigen

Benign

0.10

Eigen_PC

Benign

0.087

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.73

.;.;T

M_CAP

Benign

0.028

MetaRNN

Benign

0.26

T;T;T

MetaSVM

Benign

-0.87

MutationAssessor

Uncertain

2.3

M;M;M

PrimateAI

Uncertain

0.54

PROVEAN

Uncertain

-3.0

D;D;D

REVEL

Benign

0.15

Sift

Benign

0.13

T;T;T

Sift4G

Benign

0.17

T;T;T

Polyphen

0.67

P;P;P

Vest4

0.38

MutPred

0.29

Gain of helix (P = 0.062);Gain of helix (P = 0.062);Gain of helix (P = 0.062);

MVP

0.36

MPC

0.36

ClinPred

0.50

GERP RS

5.6

Varity_R

0.26

gMVP

0.72

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

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