7-7572548-C-G

Variant names:

• chr7-7572548-C-G
• NM_019005.4:c.73C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_019005.4(MIOS):​c.73C>G​(p.Leu25Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,824 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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: 0.0000027 (0 hom.)
• Consequence: MIOS NM_019005.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.98
• 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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21385694).

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.73C>G	p.Leu25Val	missense	Exon 4 of 13	NP_061878.3
	MIOS	NM_001370076.1		c.73C>G	p.Leu25Val	missense	Exon 3 of 12	NP_001357005.1	Q9NXC5-1
	MIOS	NM_001370077.1		c.73C>G	p.Leu25Val	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.73C>G	p.Leu25Val	missense	Exon 4 of 13	ENSP00000339881.4	Q9NXC5-1
	MIOS	ENST00000405785.5	TSL:5	c.73C>G	p.Leu25Val	missense	Exon 3 of 12	ENSP00000384088.1	Q9NXC5-1
	MIOS	ENST00000899856.1		c.73C>G	p.Leu25Val	missense	Exon 3 of 12	ENSP00000569915.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461824 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727210

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44720

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

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

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1111964

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

GnomAD4 genome Cov.: 32

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	Benign	0.23
BayesDel_addAF	Benign	-0.099	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.027	T
Eigen	Benign	-0.020
Eigen_PC	Benign	0.082
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
PhyloP100		2.0
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	0.15	N
REVEL	Benign	0.076
Sift	Uncertain	0.023	D
Sift4G	Uncertain	0.050	T
Polyphen		0.66	P
Vest4		0.69
MutPred		0.36		Gain of sheet (P = 0.0221)
MVP		0.42
MPC		0.40
ClinPred		0.34	T
GERP RS		4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.24
gMVP		0.52
Mutation Taster		=81/19	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.18		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

hg19: chr7-7612179;