22-36490072-A-G

Position:

• chr22-36490072-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001102371.2(FOXRED2):​c.1991T>C​(p.Leu664Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: FOXRED2 NM_001102371.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.33

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05510223).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FOXRED2	NM_001102371.2	c.1991T>C	p.Leu664Pro	missense_variant	9/9	ENST00000397224.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FOXRED2	ENST00000397224.9	c.1991T>C	p.Leu664Pro	missense_variant	9/9	1	NM_001102371.2	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.052
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.0030
DANN	Benign	0.33
DEOGEN2	Benign	0.00055	T;T;T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.0086	N
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.055	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	L;L;L
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.33	N;N;N
REVEL	Benign	0.0070
Sift	Benign	0.30	T;T;T
Sift4G	Benign	0.38	T;T;T
Polyphen		0.0	B;B;B
Vest4		0.086
MutPred		0.33		Gain of relative solvent accessibility (P = 0.005);Gain of relative solvent accessibility (P = 0.005);Gain of relative solvent accessibility (P = 0.005);
MVP		0.055
MPC		0.22
ClinPred		0.053	T
GERP RS		-7.7
Varity_R		0.046
gMVP		0.44

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-36886119;