Genetic Variant MN1:p.Gln309del (chr22-27799614-ATGC-A) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP3BP6BS2

The NM_002430.3(MN1):c.927_929delGCA(p.Gln309del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.000467 in 1,519,040 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign,other (no stars).

Frequency

Genomes: 𝑓 0.000060 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00051 ( 0 hom. )

Consequence

MN1
NM_002430.3 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign; other no assertion criteria provided B:1O:1

Conservation

PhyloP100: 6.72

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: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
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: Likely_benign. The variant received -6 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_002430.3

BP6

Variant 22-27799614-ATGC-A is Benign according to our data. Variant chr22-27799614-ATGC-A is described in ClinVar as Benign|other. ClinVar VariationId is 438776.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAd4 at 9 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MN1	NM_002430.3	MANE Select	c.927_929delGCA	p.Gln309del	disruptive_inframe_deletion	Exon 1 of 2	NP_002421.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MN1	ENST00000302326.5	TSL:1 MANE Select	c.927_929delGCA	p.Gln309del	disruptive_inframe_deletion	Exon 1 of 2	ENSP00000304956.4	Q10571

Frequencies

GnomAD3 genomes

AF:

0.0000600

AC:

AN:

149982

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000491

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:

0.000104

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00453

AC:

509

AN:

112286

AF XY:

0.00513

show subpopulations

Gnomad AFR exome

AF:

0.000882

Gnomad AMR exome

AF:

0.00272

Gnomad ASJ exome

AF:

0.00662

Gnomad EAS exome

AF:

0.00120

Gnomad FIN exome

AF:

0.00259

Gnomad NFE exome

AF:

0.00582

Gnomad OTH exome

AF:

0.00346

GnomAD4 exome

AF:

0.000512

AC:

701

AN:

1369058

Hom.:

AF XY:

0.000604

AC XY:

407

AN XY:

673342

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.000551

AC:

AN:

30852

American (AMR)

AF:

0.00176

AC:

AN:

33596

Ashkenazi Jewish (ASJ)

AF:

0.00183

AC:

AN:

24052

East Asian (EAS)

AF:

0.0000862

AC:

AN:

34796

South Asian (SAS)

AF:

0.00185

AC:

138

AN:

74492

European-Finnish (FIN)

AF:

0.000832

AC:

AN:

46902

Middle Eastern (MID)

AF:

0.000182

AC:

AN:

5490

European-Non Finnish (NFE)

AF:

0.000349

AC:

371

AN:

1062236

Other (OTH)

AF:

0.000512

AC:

AN:

56642

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.279

Heterozygous variant carriers

178

267

356

445

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.0000600

AC:

AN:

149982

Hom.:

Cov.:

AF XY:

0.0000956

AC XY:

AN XY:

73210

show subpopulations

African (AFR)

AF:

0.0000491

AC:

AN:

40722

American (AMR)

AF:

0.00

AC:

AN:

15118

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3456

East Asian (EAS)

AF:

0.00

AC:

AN:

5028

South Asian (SAS)

AF:

0.00

AC:

AN:

4714

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10390

Middle Eastern (MID)

AF:

0.00

AC:

AN:

304

European-Non Finnish (NFE)

AF:

0.000104

AC:

AN:

67300

Other (OTH)

AF:

0.00

AC:

AN:

2048

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.419

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:

0.0125

Hom.:

Bravo

AF:

0.0000604

ClinVar

ClinVar submissions

Significance:Benign; other

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

MN1-related disorder (1)

Hepatoblastoma (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

6.7

Mutation Taster

=72/28

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

22-27799614-ATGCTGCTGC-ATGCTGC

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