rs747503495

Variant names:

• chr22-27799614-ATGCTGCTGC-A
• rs747503495
• NM_002430.3:c.921_929delGCAGCAGCA

Your query was ambiguous. Multiple possible variants found:

• chr22-27799614-ATGCTGCTGC-A
• chr22-27799614-ATGCTGCTGC-ATGC
• chr22-27799614-ATGCTGCTGC-ATGCTGC
• chr22-27799614-ATGCTGCTGC-ATGCTGCTGCTGC
• chr22-27799614-ATGCTGCTGC-ATGCTGCTGCTGCTGC
• chr22-27799614-ATGCTGCTGC-ATGCTGCTGCTGCTGCTGC

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP3

The NM_002430.3(MN1):​c.921_929delGCAGCAGCA​(p.Gln307_Gln309del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.000000719 in 1,390,044 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: MN1 NM_002430.3 disruptive_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.72
• 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: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• familial meningioma

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP3: Nonframeshift variant in repetitive region in NM_002430.3

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MN1	NM_002430.3	c.921_929delGCAGCAGCA	p.Gln307_Gln309del	disruptive_inframe_deletion	Exon 1 of 2	ENST00000302326.5	NP_002421.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MN1	ENST00000302326.5	c.921_929delGCAGCAGCA	p.Gln307_Gln309del	disruptive_inframe_deletion	Exon 1 of 2	1	NM_002430.3	ENSP00000304956.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.19e-7 AC: 1 AN: 1390044 Hom.: 0 AF XY: 0.00000146 AC XY: 1 AN XY: 685008

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

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: 0.00 AC: 0 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: 9.31e-7 AC: 1 AN: 1074310

Other (OTH) AF: 0.00 AC: 0 AN: 57632

⚠️ 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.

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		6.7
Mutation Taster		=149/51	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;