Variant 7-7573705-G-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_019005.4(MIOS):c.1230G>C(p.Trp410Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,612,886 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

MIOS
NM_019005.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.51

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MIOS	NM_019005.4 linkuse as main transcript	c.1230G>C	p.Trp410Cys	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.1230G>C	p.Trp410Cys	missense_variant	4/13	1	NM_019005.4	P1	Q9NXC5-1
MIOS	ENST00000405785.5 linkuse as main transcript	c.1230G>C	p.Trp410Cys	missense_variant	3/12	5		P1	Q9NXC5-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1460742

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726552

show subpopulations

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:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152144

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

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

Jan 16, 2024

The c.1230G>C (p.W410C) alteration is located in exon 4 (coding exon 1) of the MIOS gene. This alteration results from a G to C substitution at nucleotide position 1230, causing the tryptophan (W) at amino acid position 410 to be replaced by a cysteine (C). 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

Pathogenic

0.94

BayesDel_addAF

Pathogenic

0.23

BayesDel_noAF

Uncertain

0.090

Cadd

Pathogenic

Dann

Uncertain

0.98

DEOGEN2

Benign

0.026

T;T

Eigen

Uncertain

0.62

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Pathogenic

0.98

M_CAP

Benign

0.024

MetaRNN

Uncertain

0.74

D;D

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

L;L

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-0.51

N;N

REVEL

Uncertain

0.40

Sift

Benign

0.17

T;T

Sift4G

Benign

0.21

T;T

Polyphen

0.96

D;D

Vest4

0.89

MutPred

0.59

Loss of MoRF binding (P = 0.0358);Loss of MoRF binding (P = 0.0358);

MVP

0.63

MPC

0.99

ClinPred

0.82

GERP RS

5.7

Varity_R

0.24

gMVP

0.83

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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