Genetic Variant MN1:p.Gln309dup (chr22-27799614-A-ATGC) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP3BP6_ModerateBS2

The NM_002430.3(MN1):c.927_929dupGCA(p.Gln309dup) variant causes a disruptive inframe insertion change. The variant allele was found at a frequency of 0.000381 in 1,540,174 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00041 ( 0 hom. )

Consequence

MN1
NM_002430.3 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 4.02

Publications

2 publications found

Variant links:

Genes affected

MN1 (HGNC:7180): (MN1 proto-oncogene, transcriptional regulator) Meningioma 1 (MN1) contains two sets of CAG repeats. It is disrupted by a balanced translocation (4;22) in a meningioma, and its inactivation may contribute to meningioma 32 pathogenesis. [provided by RefSeq, Jul 2008]

MN1 Gene-Disease associations (from GenCC):

CEBALID syndrome
Inheritance: AD Classification: STRONG Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
familial meningioma
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

MN1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -7 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_002430.3

BP6

Variant 22-27799614-A-ATGC is Benign according to our data. Variant chr22-27799614-A-ATGC is described in ClinVar as Benign. ClinVar VariationId is 2349061.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 18 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002430.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MN1	NM_002430.3	MANE Select	c.927_929dupGCA	p.Gln309dup	disruptive_inframe_insertion	Exon 1 of 2	NP_002421.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MN1	ENST00000302326.5	TSL:1 MANE Select	c.927_929dupGCA	p.Gln309dup	disruptive_inframe_insertion	Exon 1 of 2	ENSP00000304956.4

Frequencies

GnomAD3 genomes

AF:

0.000120

AC:

AN:

150022

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000982

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000198

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000199

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000134

Gnomad OTH

AF:

0.000488

GnomAD2 exomes

AF:

0.000650

AC:

AN:

112286

AF XY:

0.000555

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00256

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000240

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000392

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000409

AC:

569

AN:

1390038

Hom.:

Cov.:

AF XY:

0.000399

AC XY:

273

AN XY:

685004

show subpopulations

African (AFR)

AF:

0.0000955

AC:

AN:

31410

American (AMR)

AF:

0.00157

AC:

AN:

35088

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24638

East Asian (EAS)

AF:

0.000140

AC:

AN:

35600

South Asian (SAS)

AF:

0.000193

AC:

AN:

77836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47954

Middle Eastern (MID)

AF:

0.000359

AC:

AN:

5572

European-Non Finnish (NFE)

AF:

0.000441

AC:

474

AN:

1074308

Other (OTH)

AF:

0.000260

AC:

AN:

57632

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.443

Heterozygous variant carriers

106

132

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

110

<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:

0.000120

AC:

AN:

150136

Hom.:

Cov.:

AF XY:

0.0000954

AC XY:

AN XY:

73360

show subpopulations

African (AFR)

AF:

0.0000979

AC:

AN:

40852

American (AMR)

AF:

0.000198

AC:

AN:

15138

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3456

East Asian (EAS)

AF:

0.000199

AC:

AN:

5016

South Asian (SAS)

AF:

0.00

AC:

AN:

4708

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10398

Middle Eastern (MID)

AF:

0.00

AC:

AN:

286

European-Non Finnish (NFE)

AF:

0.000134

AC:

AN:

67310

Other (OTH)

AF:

0.000483

AC:

AN:

2070

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.522

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.0000434

Hom.:

Bravo

AF:

0.000253

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

MN1-related disorder

Benign:1

Apr 10, 2020

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

Inborn genetic diseases

Benign:1

Nov 25, 2021

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

4.0

Mutation Taster

=72/28

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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22-27799614-ATGCTGCTGC-ATGCTGCTGCTGC

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over