Variant 22-27799614-ATGCTGCTGC-ATGCTGCTGCTGC details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_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

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 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP6

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

BS2

High AC in GnomAd4 at 18 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MN1	NM_002430.3 link	c.927_929dupGCA	p.Gln309dup	disruptive_inframe_insertion	Exon 1 of 2	ENST00000302326.5	NP_002421.3	Q10571A0A024R1C3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MN1	ENST00000302326.5 link	c.927_929dupGCA	p.Gln309dup	disruptive_inframe_insertion	Exon 1 of 2	1	NM_002430.3	ENSP00000304956.4		Q10571

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

GnomAD3 exomes

AF:

0.000650

AC:

AN:

112286

Hom.:

AF XY:

0.000555

AC XY:

AN XY:

59458

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 SAS exome

AF:

0.000429

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

Gnomad4 AFR exome

AF:

0.0000955

Gnomad4 AMR exome

AF:

0.00157

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000140

Gnomad4 SAS exome

AF:

0.000193

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000441

Gnomad4 OTH exome

AF:

0.000260

GnomAD4 genome

AF:

0.000120

AC:

AN:

150136

Hom.:

Cov.:

AF XY:

0.0000954

AC XY:

AN XY:

73360

show subpopulations

Gnomad4 AFR

AF:

0.0000979

Gnomad4 AMR

AF:

0.000198

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000199

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000134

Gnomad4 OTH

AF:

0.000483

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 v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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