rs375419173

Variant names:

• chr22-50487680-C-A
• NM_017584.6:c.115C>A

Your query was ambiguous. Multiple possible variants found:

• chr22-50487680-C-A
• chr22-50487680-C-G
• chr22-50487680-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_017584.6(MIOX):​c.115C>A​(p.Arg39Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,256 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R39C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: MIOX NM_017584.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.29

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.839

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIOX	NM_017584.6	c.115C>A	p.Arg39Ser	missense_variant	Exon 3 of 10	ENST00000216075.11	NP_060054.4
MIOX	XM_011530705.3	c.115C>A	p.Arg39Ser	missense_variant	Exon 3 of 6		XP_011529007.1
MIOX	XM_047441443.1	c.115C>A	p.Arg39Ser	missense_variant	Exon 3 of 9		XP_047297399.1
MIOX	XM_005261925.5	c.-24C>A		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.115C>A	p.Arg39Ser	missense_variant	Exon 3 of 10	1	NM_017584.6	ENSP00000216075.6
MIOX	ENST00000395732.7	c.115C>A	p.Arg39Ser	missense_variant	Exon 3 of 10	1		ENSP00000379081.3
MIOX	ENST00000395733.7	c.115C>A	p.Arg39Ser	missense_variant	Exon 3 of 8	1		ENSP00000379082.3
MIOX	ENST00000451761.1	c.100C>A	p.Arg34Ser	missense_variant	Exon 2 of 9	3		ENSP00000409894.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461256 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 726930

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.85
BayesDel_addAF	Pathogenic	0.36	D
BayesDel_noAF	Pathogenic	0.28
CADD	Pathogenic	34
DANN	Uncertain	1.0
DEOGEN2	Benign	0.28	.;T;.;.
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.71	T;T;T;T
M_CAP	Benign	0.017	T
MetaRNN	Pathogenic	0.84	D;D;D;D
MetaSVM	Benign	-0.58	T
MutationAssessor	Uncertain	2.3	M;M;.;.
PrimateAI	Uncertain	0.62	T
PROVEAN	Uncertain	-3.9	D;D;D;D
REVEL	Uncertain	0.32
Sift	Benign	0.044	D;D;T;D
Sift4G	Uncertain	0.024	D;T;T;T
Polyphen		0.98	D;D;D;.
Vest4		0.73
MutPred		0.81		Loss of helix (P = 0.079);Loss of helix (P = 0.079);Loss of helix (P = 0.079);.;
MVP		0.13
MPC		0.30
ClinPred		0.99	D
GERP RS		4.4
Varity_R		0.55
gMVP		0.78

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.53		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.53		Position offset: 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: chr22-50926109;