22-50487725-G-A

Position:

• chr22-50487725-G-A

Variant summary

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

The ENST00000216075.11(MIOX):​c.160G>A​(p.Asp54Asn) 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 ENST00000216075.11 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.01

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/exons	MANE	Protein	UniProt
MIOX	NM_017584.6	c.160G>A	p.Asp54Asn	missense_variant	3/10	ENST00000216075.11	NP_060054.4
MIOX	XM_005261925.5	c.22G>A	p.Asp8Asn	missense_variant	2/9		XP_005261982.1
MIOX	XM_011530705.3	c.160G>A	p.Asp54Asn	missense_variant	3/6		XP_011529007.1
MIOX	XM_047441443.1	c.160G>A	p.Asp54Asn	missense_variant	3/9		XP_047297399.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MIOX	ENST00000216075.11	c.160G>A	p.Asp54Asn	missense_variant	3/10	1	NM_017584.6	ENSP00000216075	P1
MIOX	ENST00000395732.7	c.160G>A	p.Asp54Asn	missense_variant	3/10	1		ENSP00000379081
MIOX	ENST00000395733.7	c.160G>A	p.Asp54Asn	missense_variant	3/8	1		ENSP00000379082
MIOX	ENST00000451761.1	c.145G>A	p.Asp49Asn	missense_variant	2/9	3		ENSP00000409894

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 16, 2024

The c.160G>A (p.D54N) alteration is located in exon 3 (coding exon 3) of the MIOX gene. This alteration results from a G to A substitution at nucleotide position 160, causing the aspartic acid (D) at amino acid position 54 to be replaced by an asparagine (N). 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	Benign	0.13
BayesDel_addAF	Benign	-0.070	T
BayesDel_noAF	Benign	-0.34
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.37	.;T;.;.
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.98	D;D;D;D
M_CAP	Benign	0.016	T
MetaRNN	Uncertain	0.64	D;D;D;D
MetaSVM	Uncertain	-0.21	T
MutationAssessor	Uncertain	2.7	M;M;.;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-3.6	D;D;D;D
REVEL	Uncertain	0.41
Sift	Uncertain	0.022	D;D;D;D
Sift4G	Uncertain	0.0020	D;D;D;D
Polyphen		1.0	D;P;D;.
Vest4		0.46
MutPred		0.60		Gain of MoRF binding (P = 0.0534);Gain of MoRF binding (P = 0.0534);Gain of MoRF binding (P = 0.0534);.;
MVP		0.13
MPC		0.20
ClinPred		0.99	D
GERP RS		4.4
Varity_R		0.37
gMVP		0.56

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: chr22-50926154;