7-7574169-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_019005.4(MIOS):c.1366A>G(p.Ile456Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign 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: 7.04

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18476477).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MIOS	NM_019005.4	c.1366A>G	p.Ile456Val	missense_variant	5/13	ENST00000340080.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MIOS	ENST00000340080.9	c.1366A>G	p.Ile456Val	missense_variant	5/13	1	NM_019005.4	P1
MIOS	ENST00000405785.5	c.1366A>G	p.Ile456Val	missense_variant	4/12	5		P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 26, 2023

The c.1366A>G (p.I456V) alteration is located in exon 5 (coding exon 2) of the MIOS gene. This alteration results from a A to G substitution at nucleotide position 1366, causing the isoleucine (I) at amino acid position 456 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	Benign	0.17
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
Cadd	Benign	18
Dann	Benign	0.76
DEOGEN2	Benign	0.022	T;T
Eigen	Benign	-0.20
Eigen_PC	Benign	0.045
FATHMM_MKL	Pathogenic	0.98	D
M_CAP	Benign	0.0065	T
MetaRNN	Benign	0.18	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.54	N;N
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	0.34	N;N
REVEL	Benign	0.064
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0020	B;B
Vest4		0.39
MutPred		0.41		Loss of sheet (P = 0.0181);Loss of sheet (P = 0.0181);
MVP		0.42
MPC		0.19
ClinPred		0.98	D
GERP RS		5.4
Varity_R		0.11
gMVP		0.37

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-7613800;