chr22-50487674-C-G

Variant names:

• chr22-50487674-C-G
• NM_017584.6:c.109C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_017584.6(MIOX):​c.109C>G​(p.Leu37Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign 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: 0.556

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10759485).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIOX	NM_017584.6	c.109C>G	p.Leu37Val	missense_variant	Exon 3 of 10	ENST00000216075.11	NP_060054.4
MIOX	XM_011530705.3	c.109C>G	p.Leu37Val	missense_variant	Exon 3 of 6		XP_011529007.1
MIOX	XM_047441443.1	c.109C>G	p.Leu37Val	missense_variant	Exon 3 of 9		XP_047297399.1
MIOX	XM_005261925.5	c.-30C>G		5_prime_UTR_variant	Exon 2 of 9		XP_005261982.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MIOX	ENST00000216075.11	c.109C>G	p.Leu37Val	missense_variant	Exon 3 of 10	1	NM_017584.6	ENSP00000216075.6
MIOX	ENST00000395732.7	c.109C>G	p.Leu37Val	missense_variant	Exon 3 of 10	1		ENSP00000379081.3
MIOX	ENST00000395733.7	c.109C>G	p.Leu37Val	missense_variant	Exon 3 of 8	1		ENSP00000379082.3
MIOX	ENST00000451761.1	c.94C>G	p.Leu32Val	missense_variant	Exon 2 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

Feb 25, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.109C>G (p.L37V) alteration is located in exon 3 (coding exon 3) of the MIOX gene. This alteration results from a C to G substitution at nucleotide position 109, causing the leucine (L) at amino acid position 37 to be replaced by a valine (V). 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	0.15
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	13
DANN	Benign	0.85
DEOGEN2	Benign	0.033	.;T;.;.
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.23
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.77	T;T;T;T
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.11	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	2.0	M;M;.;.
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-0.69	N;N;N;N
REVEL	Benign	0.014
Sift	Benign	0.47	T;T;T;T
Sift4G	Benign	0.26	T;T;T;T
Polyphen		0.83	P;B;B;.
Vest4		0.41
MutPred		0.33		Gain of catalytic residue at L37 (P = 0.1189);Gain of catalytic residue at L37 (P = 0.1189);Gain of catalytic residue at L37 (P = 0.1189);.;
MVP		0.10
MPC		0.061
ClinPred		0.22	T
GERP RS		2.3
Varity_R		0.037
gMVP		0.39

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: chr22-50926103;