22-50488320-T-C

Position:

• chr22-50488320-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_017584.6(MIOX):​c.386T>C​(p.Leu129Pro) 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: 33)
• Consequence: MIOX NM_017584.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.62

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.91

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MIOX	NM_017584.6	c.386T>C	p.Leu129Pro	missense_variant	5/10	ENST00000216075.11	NP_060054.4
MIOX	XM_005261925.5	c.248T>C	p.Leu83Pro	missense_variant	4/9		XP_005261982.1
MIOX	XM_011530705.3	c.418T>C	p.Trp140Arg	missense_variant	5/6		XP_011529007.1
MIOX	XM_047441443.1	c.418T>C	p.Trp140Arg	missense_variant	5/9		XP_047297399.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MIOX	ENST00000216075.11	c.386T>C	p.Leu129Pro	missense_variant	5/10	1	NM_017584.6	ENSP00000216075.6
MIOX	ENST00000395732.7	c.386T>C	p.Leu129Pro	missense_variant	5/10	1		ENSP00000379081.3
MIOX	ENST00000395733.7	c.418T>C	p.Trp140Arg	missense_variant	5/8	1		ENSP00000379082.3
MIOX	ENST00000451761.1	c.371T>C	p.Leu124Pro	missense_variant	4/9	3		ENSP00000409894.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 04, 2023

The c.386T>C (p.L129P) alteration is located in exon 5 (coding exon 5) of the MIOX gene. This alteration results from a T to C substitution at nucleotide position 386, causing the leucine (L) at amino acid position 129 to be replaced by a proline (P). 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	0.85
BayesDel_addAF	Pathogenic	0.41	D
BayesDel_noAF	Pathogenic	0.35
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.59	D;.;.
Eigen	Uncertain	0.66
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Pathogenic	0.98	D;D;D
M_CAP	Uncertain	0.12	D
MetaRNN	Pathogenic	0.91	D;D;D
MetaSVM	Uncertain	0.026	D
PrimateAI	Uncertain	0.58	T
PROVEAN	Pathogenic	-4.4	D;D;D
REVEL	Uncertain	0.39
Sift	Uncertain	0.0010	D;D;D
Sift4G	Uncertain	0.0020	D;T;D
Polyphen		0.16	B;P;.
Vest4		0.92
MutPred		0.79		Loss of sheet (P = 0.0228);Loss of sheet (P = 0.0228);.;
MVP		0.32
MPC		0.16
ClinPred		0.99	D
GERP RS		4.4
Varity_R		0.96
gMVP		0.93

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: chr22-50926749;