chr22-50487701-C-T

Variant names:

• chr22-50487701-C-T
• rs1049083027
• NM_017584.6:c.136C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_017584.6(MIOX):​c.136C>T​(p.Leu46Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,524 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: MIOX NM_017584.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.73
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3358782).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017584.6. 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
	MIOX	NM_017584.6	MANE Select	c.136C>T	p.Leu46Phe	missense	Exon 3 of 10	NP_060054.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIOX	ENST00000216075.11	TSL:1 MANE Select	c.136C>T	p.Leu46Phe	missense	Exon 3 of 10	ENSP00000216075.6	Q9UGB7-1
	MIOX	ENST00000395732.7	TSL:1	c.136C>T	p.Leu46Phe	missense	Exon 3 of 10	ENSP00000379081.3	A6PVH2
	MIOX	ENST00000395733.7	TSL:1	c.136C>T	p.Leu46Phe	missense	Exon 3 of 8	ENSP00000379082.3	Q9UGB7-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461524 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727074

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53140

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111960

Other (OTH) AF: 0.00 AC: 0 AN: 60386

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	0.010	T
BayesDel_noAF	Benign	-0.22
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.44	T
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.34	T
MetaSVM	Uncertain	-0.27	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		1.7
PrimateAI	Benign	0.48	T
PROVEAN	Uncertain	-2.4	N
REVEL	Uncertain	0.31
Sift	Uncertain	0.028	D
Sift4G	Uncertain	0.026	D
Polyphen		1.0	D
Vest4		0.41
MutPred		0.46		Gain of catalytic residue at L46 (P = 0.0117)
MVP		0.17
MPC		0.27
ClinPred		0.98	D
GERP RS		4.4
PromoterAI		-0.015	Neutral
Varity_R		0.15
gMVP		0.49
Mutation Taster		=64/36	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1049083027; hg19: chr22-50926130;