rs1555065162

Variant names:

• chr11-126274958-C-A
• rs1555065162
• NM_017547.4:c.568C>A

Your query was ambiguous. Multiple possible variants found:

• chr11-126274958-C-A
• chr11-126274958-C-G
• chr11-126274958-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_017547.4(FOXRED1):​c.568C>A​(p.Pro190Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P190S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: FOXRED1 NM_017547.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.32
• Publications: 0 publications found

Genes affected

FOXRED1 (HGNC:26927): (FAD dependent oxidoreductase domain containing 1) This gene encodes a protein that contains a FAD-dependent oxidoreductase domain. The encoded protein is localized to the mitochondria and may function as a chaperone protein required for the function of mitochondrial complex I. Mutations in this gene are associated with mitochondrial complex I deficiency. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Dec 2010]

FOXRED1 Gene-Disease associations (from GenCC):

• mitochondrial complex I deficiency, nuclear type 19

  Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
• mitochondrial disease

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• mitochondrial complex I deficiency, nuclear type 1

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• Leigh syndrome

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen, Laboratory for Molecular Medicine
• Leigh syndrome with leukodystrophy

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• mitochondrial complex I deficiency

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.865

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXRED1	NM_017547.4	c.568C>A	p.Pro190Thr	missense_variant	Exon 5 of 11	ENST00000263578.10	NP_060017.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXRED1	ENST00000263578.10	c.568C>A	p.Pro190Thr	missense_variant	Exon 5 of 11	1	NM_017547.4	ENSP00000263578.5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.27	T;.
Eigen	Pathogenic	0.72
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.88	D;D
M_CAP	Pathogenic	0.34	D
MetaRNN	Pathogenic	0.86	D;D
MetaSVM	Uncertain	0.57	D
MutationAssessor	Pathogenic	3.8	H;.
PhyloP100		5.3
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-3.5	D;D
REVEL	Pathogenic	0.71
Sift	Uncertain	0.014	D;D
Sift4G	Uncertain	0.028	D;D
Polyphen		0.97	D;D
Vest4		0.79
MutPred		0.59		Loss of stability (P = 0.0417);.;
MVP		0.95
MPC		0.56
ClinPred		0.99	D
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.67
gMVP		0.84
Mutation Taster		=72/28	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1555065162; hg19: chr11-126144853;