7-7572971-G-A

Variant summary

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

The NM_019005.4(MIOS):c.496G>A(p.Gly166Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,814 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: MIOS NM_019005.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.39

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=0.17353809).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MIOS	NM_019005.4	c.496G>A	p.Gly166Ser	missense_variant	4/13	ENST00000340080.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MIOS	ENST00000340080.9	c.496G>A	p.Gly166Ser	missense_variant	4/13	1	NM_019005.4	P1
MIOS	ENST00000405785.5	c.496G>A	p.Gly166Ser	missense_variant	3/12	5		P1
MIOS	ENST00000456533.1	c.496G>A	p.Gly166Ser	missense_variant	2/2	3
MIOS	ENST00000433635.1			downstream_gene_variant		2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461814 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 727196

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.00

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

Oct 05, 2023

The c.496G>A (p.G166S) alteration is located in exon 4 (coding exon 1) of the MIOS gene. This alteration results from a G to A substitution at nucleotide position 496, causing the glycine (G) at amino acid position 166 to be replaced by a serine (S). 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	0.068
BayesDel_addAF	Benign	-0.092	T
BayesDel_noAF	Benign	-0.37
Cadd	Benign	22
Dann	Uncertain	0.98
DEOGEN2	Benign	0.015	T;T;T
Eigen	Benign	-0.023
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.95	D
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.17	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L;L;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-0.050	N;N;N
REVEL	Benign	0.12
Sift	Benign	0.33	T;T;T
Sift4G	Benign	0.75	T;T;T
Polyphen		0.029	B;B;.
Vest4		0.39
MutPred		0.39		Gain of disorder (P = 0.062);Gain of disorder (P = 0.062);Gain of disorder (P = 0.062);
MVP		0.40
MPC		0.24
ClinPred		0.60	D
GERP RS		5.8
Varity_R		0.077
gMVP		0.18

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: chr7-7612602;