chr22-50489911-G-C

Position:

• chr22-50489911-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017584.6(MIOX):​c.*55G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.333 in 1,534,558 control chromosomes in the GnomAD database, including 88,026 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.27 (6423 hom., cov: 34)
  • Exomes 𝑓: 0.34 (81603 hom.)
• Consequence: MIOX NM_017584.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.60

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.35 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MIOX	NM_017584.6	c.*55G>C		3_prime_UTR_variant	10/10	ENST00000216075.11	NP_060054.4
MIOX	XM_005261925.5	c.*55G>C		3_prime_UTR_variant	9/9		XP_005261982.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MIOX	ENST00000216075.11	c.*55G>C		3_prime_UTR_variant	10/10	1	NM_017584.6	ENSP00000216075.6
MIOX	ENST00000395732.7	c.*86G>C		3_prime_UTR_variant	10/10	1		ENSP00000379081.3
MIOX	ENST00000395733.7	c.*86G>C		3_prime_UTR_variant	8/8	1		ENSP00000379082.3
MIOX	ENST00000451761.1	c.*55G>C		3_prime_UTR_variant	9/9	3		ENSP00000409894.1

Frequencies

GnomAD3 genomes AF: 0.270 AC: 40990 AN: 152090 Hom.: 6423 Cov.: 34

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.301

Gnomad AMR AF: 0.284

Gnomad ASJ AF: 0.342

Gnomad EAS AF: 0.325

Gnomad SAS AF: 0.229

Gnomad FIN AF: 0.265

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.354

Gnomad OTH AF: 0.294

GnomAD4 exome AF: 0.339 AC: 469258 AN: 1382350 Hom.: 81603 Cov.: 22 AF XY: 0.337 AC XY: 232940 AN XY: 691304

Gnomad4 AFR exome AF: 0.110

Gnomad4 AMR exome AF: 0.315

Gnomad4 ASJ exome AF: 0.343

Gnomad4 EAS exome AF: 0.348

Gnomad4 SAS exome AF: 0.242

Gnomad4 FIN exome AF: 0.281

Gnomad4 NFE exome AF: 0.358

Gnomad4 OTH exome AF: 0.324

GnomAD4 genome AF: 0.269 AC: 40990 AN: 152208 Hom.: 6423 Cov.: 34 AF XY: 0.264 AC XY: 19650 AN XY: 74404

Gnomad4 AFR AF: 0.117

Gnomad4 AMR AF: 0.283

Gnomad4 ASJ AF: 0.342

Gnomad4 EAS AF: 0.326

Gnomad4 SAS AF: 0.229

Gnomad4 FIN AF: 0.265

Gnomad4 NFE AF: 0.354

Gnomad4 OTH AF: 0.290

Alfa AF: 0.214 Hom.: 571

Bravo AF: 0.271

Asia WGS AF: 0.240 AC: 835 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.1
DANN	Benign	0.32

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

LitVar

Other links and lift over

dbSNP: rs1055271; hg19: chr22-50928340; COSMIC: COSV53311651; COSMIC: COSV53311651;