rs1555065162

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_017547.4(FOXRED1):​c.568C>T​(p.Pro190Ser) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: FOXRED1 NM_017547.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:2
• 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: Laboratory for Molecular Medicine, ClinGen
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.774

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017547.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXRED1	NM_017547.4	MANE Select	c.568C>T	p.Pro190Ser	missense	Exon 5 of 11	NP_060017.1	Q96CU9-1
	FOXRED1	NM_001425160.1		c.598C>T	p.Pro200Ser	missense	Exon 5 of 11	NP_001412089.1
	FOXRED1	NM_001425161.1		c.568C>T	p.Pro190Ser	missense	Exon 5 of 11	NP_001412090.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXRED1	ENST00000263578.10	TSL:1 MANE Select	c.568C>T	p.Pro190Ser	missense	Exon 5 of 11	ENSP00000263578.5	Q96CU9-1
	FOXRED1	ENST00000534315.5	TSL:1	n.944-369C>T		intron	N/A
	FOXRED1	ENST00000853296.1		c.598C>T	p.Pro200Ser	missense	Exon 5 of 11	ENSP00000523355.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Leigh syndrome (1)
-	1	-	Mitochondrial complex I deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.079	D
BayesDel_noAF	Benign	-0.12
CADD	Uncertain	23
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.26	T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.89	D
M_CAP	Uncertain	0.25	D
MetaRNN	Pathogenic	0.77	D
MetaSVM	Uncertain	0.34	D
MutationAssessor	Uncertain	2.2	M
PhyloP100		5.3
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-3.1	D
REVEL	Uncertain	0.57
Sift	Benign	0.13	T
Sift4G	Benign	0.11	T
Polyphen		0.77	P
Vest4		0.67
MutPred		0.56		Gain of MoRF binding (P = 0.0471)
MVP		0.91
MPC		0.26
ClinPred		0.92	D
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.35
gMVP		0.85
Mutation Taster		=77/23	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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;