7-7573487-A-G

Variant names:

• chr7-7573487-A-G
• rs201095729
• NM_019005.4:c.1012A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_019005.4(MIOS):​c.1012A>G​(p.Met338Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000266 in 1,614,150 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000089 (0 hom.)
• Consequence: MIOS NM_019005.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.88
• Publications: 0 publications found

Genes affected

MIOS (HGNC:21905): (meiosis regulator for oocyte development) Involved in cellular response to amino acid starvation; positive regulation of TOR signaling; and protein-containing complex localization. Located in several cellular components, including cytosol; lysosomal membrane; and nucleoplasm. Part of GATOR2 complex. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000293795 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019005.4. 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
	MIOS	NM_019005.4	MANE Select	c.1012A>G	p.Met338Val	missense	Exon 4 of 13	NP_061878.3
	MIOS	NM_001370076.1		c.1012A>G	p.Met338Val	missense	Exon 3 of 12	NP_001357005.1	Q9NXC5-1
	MIOS	NM_001370077.1		c.1012A>G	p.Met338Val	missense	Exon 2 of 11	NP_001357006.1	Q9NXC5-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIOS	ENST00000340080.9	TSL:1 MANE Select	c.1012A>G	p.Met338Val	missense	Exon 4 of 13	ENSP00000339881.4	Q9NXC5-1
	MIOS	ENST00000405785.5	TSL:5	c.1012A>G	p.Met338Val	missense	Exon 3 of 12	ENSP00000384088.1	Q9NXC5-1
	MIOS	ENST00000899856.1		c.1012A>G	p.Met338Val	missense	Exon 3 of 12	ENSP00000569915.1

Frequencies

GnomAD3 genomes AF: 0.000197 AC: 30 AN: 152198 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000724

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000441 AC: 11 AN: 249474 AF XY: 0.0000369

Gnomad AFR exome AF: 0.000710

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000889 AC: 13 AN: 1461834 Hom.: 0 Cov.: 32 AF XY: 0.00000688 AC XY: 5 AN XY: 727212

African (AFR) AF: 0.000388 AC: 13 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111962

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome AF: 0.000197 AC: 30 AN: 152316 Hom.: 0 Cov.: 32 AF XY: 0.000201 AC XY: 15 AN XY: 74490

African (AFR) AF: 0.000722 AC: 30 AN: 41572

American (AMR) AF: 0.00 AC: 0 AN: 15306

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.0000609 Hom.: 0

Bravo AF: 0.000166

ESP6500AA AF: 0.000767 AC: 3

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000744 AC: 9

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	Uncertain	0.49
BayesDel_addAF	Uncertain	0.039	T
BayesDel_noAF	Pathogenic	0.19
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.074	T
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.028	D
MetaRNN	Uncertain	0.46	T
MetaSVM	Benign	-0.76	T
MutationAssessor	Benign	1.5	L
PhyloP100		8.9
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-2.2	N
REVEL	Uncertain	0.36
Sift	Uncertain	0.014	D
Sift4G	Benign	0.10	T
Polyphen		0.34	B
Vest4		0.93
MVP		0.71
MPC		0.39
ClinPred		0.20	T
GERP RS		5.6
Varity_R		0.34
gMVP		0.58
Mutation Taster		=75/25	polymorphism

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

Other links and lift over

dbSNP: rs201095729; hg19: chr7-7613118;