22-50488006-T-C

Variant names:

• chr22-50488006-T-C
• NM_017584.6:c.298T>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_017584.6(MIOX):​c.298T>C​(p.Phe100Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: MIOX NM_017584.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.87

Genes affected

MIOX (HGNC:14522): (myo-inositol oxygenase) Enables ferric iron binding activity and inositol oxygenase activity. Involved in inositol catabolic process. Predicted to be located in cytoplasm and inclusion body. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIOX	NM_017584.6	c.298T>C	p.Phe100Leu	missense_variant	Exon 4 of 10	ENST00000216075.11	NP_060054.4
MIOX	XM_005261925.5	c.160T>C	p.Phe54Leu	missense_variant	Exon 3 of 9		XP_005261982.1
MIOX	XM_011530705.3	c.298T>C	p.Phe100Leu	missense_variant	Exon 4 of 6		XP_011529007.1
MIOX	XM_047441443.1	c.298T>C	p.Phe100Leu	missense_variant	Exon 4 of 9		XP_047297399.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MIOX	ENST00000216075.11	c.298T>C	p.Phe100Leu	missense_variant	Exon 4 of 10	1	NM_017584.6	ENSP00000216075.6
MIOX	ENST00000395732.7	c.298T>C	p.Phe100Leu	missense_variant	Exon 4 of 10	1		ENSP00000379081.3
MIOX	ENST00000395733.7	c.298T>C	p.Phe100Leu	missense_variant	Exon 4 of 8	1		ENSP00000379082.3
MIOX	ENST00000451761.1	c.283T>C	p.Phe95Leu	missense_variant	Exon 3 of 9	3		ENSP00000409894.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 14, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.298T>C (p.F100L) alteration is located in exon 4 (coding exon 4) of the MIOX gene. This alteration results from a T to C substitution at nucleotide position 298, causing the phenylalanine (F) at amino acid position 100 to be replaced by a leucine (L). 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	Pathogenic	0.98
BayesDel_addAF	Uncertain	0.026	T
BayesDel_noAF	Benign	-0.20
CADD	Pathogenic	26
DANN	Uncertain	0.98
DEOGEN2	Benign	0.37	.;T;.;.
Eigen	Benign	0.14
Eigen_PC	Benign	0.22
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.95	D;D;D;D
M_CAP	Benign	0.0066	T
MetaRNN	Uncertain	0.57	D;D;D;D
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.69	N;N;.;.
PrimateAI	Uncertain	0.66	T
PROVEAN	Pathogenic	-5.4	D;D;D;D
REVEL	Uncertain	0.40
Sift	Benign	0.94	T;T;T;T
Sift4G	Benign	0.083	T;T;T;T
Polyphen		1.0	D;P;P;.
Vest4		0.66
MutPred		0.56		Gain of helix (P = 0.132);Gain of helix (P = 0.132);Gain of helix (P = 0.132);.;
MVP		0.095
MPC		0.33
ClinPred		0.95	D
GERP RS		4.2
Varity_R		0.84
gMVP		0.64

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: chr22-50926435;