22-27799614-ATGCTGCTGC-ATGCTGCTGCTGCTGCTGC

Variant names:

• chr22-27799614-A-ATGCTGCTGC
• rs747503495
• NM_002430.3:c.921_929dupGCAGCAGCA

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP3 BS2

The NM_002430.3(MN1):​c.921_929dupGCAGCAGCA​(p.Gln307_Gln309dup) variant causes a disruptive inframe insertion change. The variant allele was found at a frequency of 0.0000194 in 1,390,046 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000019 (0 hom.)
• Consequence: MN1 NM_002430.3 disruptive_inframe_insertion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.02
• Publications: 2 publications found

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

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_002430.3
• BS2: High AC in GnomAdExome4 at 27 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.921_929dupGCAGCAGCA	p.Gln307_Gln309dup	disruptive_inframe_insertion	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.921_929dupGCAGCAGCA	p.Gln307_Gln309dup	disruptive_inframe_insertion	Exon 1 of 2	ENSP00000304956.4	Q10571

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.0000194 AC: 27 AN: 1390046 Hom.: 0 Cov.: 33 AF XY: 0.0000146 AC XY: 10 AN XY: 685010

African (AFR) AF: 0.00 AC: 0 AN: 31410

American (AMR) AF: 0.00 AC: 0 AN: 35088

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24638

East Asian (EAS) AF: 0.000112 AC: 4 AN: 35600

South Asian (SAS) AF: 0.00 AC: 0 AN: 77836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47958

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5572

European-Non Finnish (NFE) AF: 0.0000205 AC: 22 AN: 1074312

Other (OTH) AF: 0.0000174 AC: 1 AN: 57632

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	CEBALID syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.0
Mutation Taster		=72/28	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs747503495; hg19: chr22-28195602;