7-7573073-C-G

Variant names:

• chr7-7573073-C-G
• rs1783407684
• NM_019005.4:c.598C>G

Variant summary

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

The NM_019005.4(MIOS):​c.598C>G​(p.Leu200Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MIOS NM_019005.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.80

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]

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, 0.775

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIOS	NM_019005.4	c.598C>G	p.Leu200Val	missense_variant	Exon 4 of 13	ENST00000340080.9	NP_061878.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MIOS	ENST00000340080.9	c.598C>G	p.Leu200Val	missense_variant	Exon 4 of 13	1	NM_019005.4	ENSP00000339881.4
MIOS	ENST00000405785.5	c.598C>G	p.Leu200Val	missense_variant	Exon 3 of 12	5		ENSP00000384088.1
MIOS	ENST00000456533.1	c.*60C>G		downstream_gene_variant		3		ENSP00000410752.1
MIOS	ENST00000433635.1	c.*148C>G		downstream_gene_variant		2		ENSP00000413050.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 06, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.598C>G (p.L200V) alteration is located in exon 4 (coding exon 1) of the MIOS gene. This alteration results from a C to G substitution at nucleotide position 598, causing the leucine (L) at amino acid position 200 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.084	T;T
Eigen	Uncertain	0.62
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.91	.;D
M_CAP	Benign	0.024	T
MetaRNN	Pathogenic	0.77	D;D
MetaSVM	Benign	-0.52	T
MutationAssessor	Benign	2.0	M;M
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-1.4	N;N
REVEL	Uncertain	0.31
Sift	Benign	0.073	T;T
Sift4G	Uncertain	0.015	D;D
Polyphen		0.85	P;P
Vest4		0.81
MutPred		0.45		Gain of catalytic residue at L200 (P = 0.0028);Gain of catalytic residue at L200 (P = 0.0028);
MVP		0.69
MPC		0.78
ClinPred		0.87	D
GERP RS		5.8
Varity_R		0.20
gMVP		0.46

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: rs1783407684; hg19: chr7-7612704;