chr22-50487464-C-T

Variant names:

• chr22-50487464-C-T
• rs373424607
• NM_017584.6:c.95C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_017584.6(MIOX):​c.95C>T​(p.Thr32Met) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000304 in 1,613,168 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000079 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000025 (0 hom.)
• Consequence: MIOX NM_017584.6 missense, splice_region
• Scores: Splicing: ADA: 0.00009284
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.957
• Publications: 1 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.07459065).

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.95C>T	p.Thr32Met	missense splice_region	Exon 2 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.95C>T	p.Thr32Met	missense splice_region	Exon 2 of 10	ENSP00000216075.6	Q9UGB7-1
	MIOX	ENST00000395732.7	TSL:1	c.95C>T	p.Thr32Met	missense splice_region	Exon 2 of 10	ENSP00000379081.3	A6PVH2
	MIOX	ENST00000395733.7	TSL:1	c.95C>T	p.Thr32Met	missense splice_region	Exon 2 of 8	ENSP00000379082.3	Q9UGB7-2

Frequencies

GnomAD3 genomes AF: 0.0000790 AC: 12 AN: 151974 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000266

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000599 AC: 15 AN: 250404 AF XY: 0.0000591

Gnomad AFR exome AF: 0.000555

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000100

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000354

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.0000253 AC: 37 AN: 1461076 Hom.: 0 Cov.: 32 AF XY: 0.0000261 AC XY: 19 AN XY: 726896

African (AFR) AF: 0.000329 AC: 11 AN: 33462

American (AMR) AF: 0.00 AC: 0 AN: 44662

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26094

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86216

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53252

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5756

European-Non Finnish (NFE) AF: 0.0000207 AC: 23 AN: 1111580

Other (OTH) AF: 0.00 AC: 0 AN: 60356

GnomAD4 genome AF: 0.0000789 AC: 12 AN: 152092 Hom.: 0 Cov.: 33 AF XY: 0.000108 AC XY: 8 AN XY: 74354

African (AFR) AF: 0.000265 AC: 11 AN: 41520

American (AMR) AF: 0.00 AC: 0 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67920

Other (OTH) AF: 0.00 AC: 0 AN: 2104

Alfa AF: 0.0000761 Hom.: 0

Bravo AF: 0.0000982

ExAC AF: 0.0000906 AC: 11

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	0.11
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	16
DANN	Uncertain	1.0
DEOGEN2	Benign	0.18	T
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.35
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.0038	T
MetaRNN	Benign	0.075	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.9	L
PhyloP100		0.96
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.055
Sift	Uncertain	0.028	D
Sift4G	Uncertain	0.031	D
Polyphen		1.0	D
Vest4		0.31
MVP		0.13
MPC		0.059
ClinPred		0.61	D
GERP RS		-0.16
PromoterAI		-0.0097	Neutral
Varity_R		0.026
gMVP		0.50
Mutation Taster		=86/14	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000093
dbscSNV1_RF	Benign	0.046
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

Other links and lift over

dbSNP: rs373424607; hg19: chr22-50925893; COSMIC: COSV53311864; COSMIC: COSV53311864;