Genetic Variant MIOS:c.2531+104A>G (chr7-7606175-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_019005.4(MIOS):c.2531+104A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.686 in 1,415,508 control chromosomes in the GnomAD database, including 336,313 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.63 ( 31195 hom., cov: 32)

Exomes 𝑓: 0.69 ( 305118 hom. )

Consequence

MIOS
NM_019005.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.156

Publications

6 publications found

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:

ENSG00000293795 (HGNC:):

ENSG00000293795 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.74 is higher than 0.05.

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MIOS	NM_019005.4	MANE Select	c.2531+104A>G	intron	N/A	NP_061878.3
MIOS	NM_001370076.1		c.2531+104A>G	intron	N/A	NP_001357005.1	Q9NXC5-1
MIOS	NM_001370077.1		c.2531+104A>G	intron	N/A	NP_001357006.1	Q9NXC5-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MIOS	ENST00000340080.9	TSL:1 MANE Select	c.2531+104A>G	intron	N/A	ENSP00000339881.4	Q9NXC5-1
MIOS	ENST00000493227.1	TSL:1	n.1302+104A>G	intron	N/A
MIOS	ENST00000405785.5	TSL:5	c.2531+104A>G	intron	N/A	ENSP00000384088.1	Q9NXC5-1

Frequencies

GnomAD3 genomes

AF:

0.631

AC:

95790

AN:

151864

Hom.:

31181

Cov.:

show subpopulations

Gnomad AFR

AF:

0.453

Gnomad AMI

AF:

0.808

Gnomad AMR

AF:

0.751

Gnomad ASJ

AF:

0.636

Gnomad EAS

AF:

0.664

Gnomad SAS

AF:

0.669

Gnomad FIN

AF:

0.672

Gnomad MID

AF:

0.570

Gnomad NFE

AF:

0.697

Gnomad OTH

AF:

0.646

GnomAD4 exome

AF:

0.692

AC:

874638

AN:

1263526

Hom.:

305118

AF XY:

0.693

AC XY:

431833

AN XY:

623504

show subpopulations

African (AFR)

AF:

0.435

AC:

12330

AN:

28334

American (AMR)

AF:

0.793

AC:

24096

AN:

30380

Ashkenazi Jewish (ASJ)

AF:

0.650

AC:

13043

AN:

20062

East Asian (EAS)

AF:

0.628

AC:

23629

AN:

37654

South Asian (SAS)

AF:

0.672

AC:

42335

AN:

62968

European-Finnish (FIN)

AF:

0.678

AC:

31823

AN:

46970

Middle Eastern (MID)

AF:

0.615

AC:

3140

AN:

5104

European-Non Finnish (NFE)

AF:

0.703

AC:

688630

AN:

979564

Other (OTH)

AF:

0.678

AC:

35612

AN:

52490

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

12614

25228

37841

50455

63069

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17746

35492

53238

70984

88730

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.631

AC:

95830

AN:

151982

Hom.:

31195

Cov.:

AF XY:

0.632

AC XY:

46962

AN XY:

74318

show subpopulations

African (AFR)

AF:

0.453

AC:

18759

AN:

41426

American (AMR)

AF:

0.752

AC:

11477

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.636

AC:

2208

AN:

3470

East Asian (EAS)

AF:

0.664

AC:

3426

AN:

5158

South Asian (SAS)

AF:

0.669

AC:

3231

AN:

4828

European-Finnish (FIN)

AF:

0.672

AC:

7101

AN:

10562

Middle Eastern (MID)

AF:

0.571

AC:

168

AN:

294

European-Non Finnish (NFE)

AF:

0.697

AC:

47380

AN:

67966

Other (OTH)

AF:

0.638

AC:

1343

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1718

3435

5153

6870

8588

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

780

1560

2340

3120

3900

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.684

Hom.:

38956

Bravo

AF:

0.633

Asia WGS

AF:

0.607

AC:

2111

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

2.1

(source)

DANN

Benign

0.67

PhyloP100

0.16

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over