Variant 7-7572930-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_019005.4(MIOS):c.455C>A(p.Thr152Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 1,461,834 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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: 0.0000068 ( 0 hom. )

Consequence

MIOS
NM_019005.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.47

Variant links:

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]

MIOS links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.07758081).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MIOS	NM_019005.4 linkuse as main transcript	c.455C>A	p.Thr152Asn	missense_variant	4/13	ENST00000340080.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MIOS	ENST00000340080.9 linkuse as main transcript	c.455C>A	p.Thr152Asn	missense_variant	4/13	1	NM_019005.4	P1	Q9NXC5-1
MIOS	ENST00000405785.5 linkuse as main transcript	c.455C>A	p.Thr152Asn	missense_variant	3/12	5		P1	Q9NXC5-1
MIOS	ENST00000456533.1 linkuse as main transcript	c.455C>A	p.Thr152Asn	missense_variant	2/2	3
MIOS	ENST00000433635.1 linkuse as main transcript			downstream_gene_variant		2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000802

AC:

AN:

249306

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135272

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000579

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS 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:

0.00000684

AC:

AN:

1461834

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727222

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000447

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:

0.00000719

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.00000828

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 06, 2021

The c.455C>A (p.T152N) alteration is located in exon 4 (coding exon 1) of the MIOS gene. This alteration results from a C to A substitution at nucleotide position 455, causing the threonine (T) at amino acid position 152 to be replaced by an asparagine (N). 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

0.078

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.53

Cadd

Benign

Dann

Benign

0.95

DEOGEN2

Benign

0.033

T;T;T

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.16

FATHMM_MKL

Benign

0.59

M_CAP

Benign

0.0045

MetaRNN

Benign

0.078

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.55

N;N;.

MutationTaster

Benign

0.79

N;N

PrimateAI

Benign

0.44

PROVEAN

Benign

-0.51

N;N;N

REVEL

Benign

0.032

Sift

Benign

0.20

T;T;D

Sift4G

Benign

0.54

T;T;T

Polyphen

0.0020

B;B;.

Vest4

0.25

MutPred

0.32

Loss of phosphorylation at T152 (P = 0.0722);Loss of phosphorylation at T152 (P = 0.0722);Loss of phosphorylation at T152 (P = 0.0722);

MVP

0.18

MPC

0.28

ClinPred

0.074

GERP RS

3.9

Varity_R

0.11

gMVP

0.14

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over