22-27750781-GAA-GAAAA

Variant names:

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

Variant summary

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

The NM_002430.3(MN1):​c.*132_*133dupTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00324 in 494,234 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 0.000048 (0 hom., cov: 23)
  • Exomes 𝑓: 0.0035 (0 hom.)
• Consequence: MN1 NM_002430.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0310
• 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_*133dupTT		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_*133dupTT		3_prime_UTR	Exon 2 of 2	ENSP00000304956.4	Q10571
	MN1	ENST00000497225.1	TSL:1	n.451_452dupTT		non_coding_transcript_exon	Exon 2 of 2
	MN1	ENST00000424656.1	TSL:5	n.*132_*133dupTT		non_coding_transcript_exon	Exon 2 of 3	ENSP00000397805.1	H7C105

Frequencies

GnomAD3 genomes AF: 0.0000483 AC: 2 AN: 41410 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: 0.00188

GnomAD4 exome AF: 0.00354 AC: 1601 AN: 452824 Hom.: 0 Cov.: 6 AF XY: 0.00353 AC XY: 806 AN XY: 228204

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

African (AFR) AF: 0.000802 AC: 9 AN: 11222

American (AMR) AF: 0.00183 AC: 17 AN: 9312

Ashkenazi Jewish (ASJ) AF: 0.00585 AC: 60 AN: 10250

East Asian (EAS) AF: 0.00723 AC: 159 AN: 21988

South Asian (SAS) AF: 0.00435 AC: 112 AN: 25756

European-Finnish (FIN) AF: 0.00382 AC: 106 AN: 27742

Middle Eastern (MID) AF: 0.00175 AC: 3 AN: 1710

European-Non Finnish (NFE) AF: 0.00330 AC: 1065 AN: 322514

Other (OTH) AF: 0.00313 AC: 70 AN: 22330

⚠️ 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: 0.0000483 AC: 2 AN: 41410 Hom.: 0 Cov.: 23 AF XY: 0.0000511 AC XY: 1 AN XY: 19566

⚠️ 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: 2820

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: 2238

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

European-Non Finnish (NFE) AF: 0.0000476 AC: 1 AN: 21006

Other (OTH) AF: 0.00188 AC: 1 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.

Alfa AF: 0.00 Hom.: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.031

Splicing

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

Other links and lift over

dbSNP: rs377485634; hg19: chr22-28146769;