chr22-27750781-GAA-G

Variant names:

• chr22-27750781-GAA-G
• rs377485634
• NM_002430.3:c.*132_*133delTT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_002430.3(MN1):​c.*132_*133delTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000884 in 497,830 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), which may indicate mosaicism or somatic mutations in the reference population data. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000024 (0 hom., cov: 23)
  • Exomes 𝑓: 0.000094 (0 hom.)
• Consequence: MN1 NM_002430.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.395
• Publications: 0 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, Labcorp Genetics (formerly Invitae), Ambry Genetics
• familial meningioma

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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.*132_*133delTT		3_prime_UTR	Exon 2 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.*132_*133delTT		3_prime_UTR	Exon 2 of 2	ENSP00000304956.4	Q10571
	MN1	ENST00000497225.1	TSL:1	n.451_452delTT		non_coding_transcript_exon	Exon 2 of 2
	MN1	ENST00000424656.1	TSL:5	n.*132_*133delTT		non_coding_transcript_exon	Exon 2 of 3	ENSP00000397805.1	H7C105

Frequencies

GnomAD3 genomes AF: 0.0000241 AC: 1 AN: 41416 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00

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: 0.0000476

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000942 AC: 43 AN: 456414 Hom.: 0 AF XY: 0.0000956 AC XY: 22 AN XY: 230062

⚠️ 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: 11266

American (AMR) AF: 0.000106 AC: 1 AN: 9436

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10330

East Asian (EAS) AF: 0.0000449 AC: 1 AN: 22254

South Asian (SAS) AF: 0.0000384 AC: 1 AN: 26012

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28050

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1718

European-Non Finnish (NFE) AF: 0.000123 AC: 40 AN: 324838

Other (OTH) AF: 0.00 AC: 0 AN: 22510

⚠️ 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 AF: 0.0000241 AC: 1 AN: 41416 Hom.: 0 Cov.: 23 AF XY: 0.0000511 AC XY: 1 AN XY: 19570

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

African (AFR) AF: 0.00 AC: 0 AN: 10162

American (AMR) AF: 0.00 AC: 0 AN: 2822

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1120

East Asian (EAS) AF: 0.00 AC: 0 AN: 1940

South Asian (SAS) AF: 0.00 AC: 0 AN: 1282

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2240

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 38

European-Non Finnish (NFE) AF: 0.0000476 AC: 1 AN: 21008

Other (OTH) AF: 0.00 AC: 0 AN: 532

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.40
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs377485634; hg19: chr22-28146769;