22-27750781-G-GA

Variant names:

• chr22-27750781-G-GA
• rs377485634
• NM_002430.3:c.*133dupT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_002430.3(MN1):​c.*133dupT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 463,614 control chromosomes in the GnomAD database, including 80 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.076 (52 hom., cov: 23)
  • Exomes 𝑓: 0.12 (28 hom.)
• Consequence: MN1 NM_002430.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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: Benign. The variant received -10 ACMG points.

• BP6: Variant 22-27750781-G-GA is Benign according to our data. Variant chr22-27750781-G-GA is described in ClinVar as Benign. ClinVar VariationId is 1261235.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

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.*133dupT		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.*133dupT		3_prime_UTR	Exon 2 of 2	ENSP00000304956.4	Q10571
	MN1	ENST00000497225.1	TSL:1	n.452dupT		non_coding_transcript_exon	Exon 2 of 2
	MN1	ENST00000424656.1	TSL:5	n.*133dupT		non_coding_transcript_exon	Exon 2 of 3	ENSP00000397805.1	H7C105

Frequencies

GnomAD3 genomes AF: 0.0758 AC: 3129 AN: 41258 Hom.: 52 Cov.: 23

Gnomad AFR AF: 0.0152

Gnomad AMI AF: 0.0184

Gnomad AMR AF: 0.0413

Gnomad ASJ AF: 0.206

Gnomad EAS AF: 0.204

Gnomad SAS AF: 0.0273

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.105

Gnomad NFE AF: 0.0878

Gnomad OTH AF: 0.0625

GnomAD4 exome AF: 0.122 AC: 51642 AN: 422328 Hom.: 28 Cov.: 6 AF XY: 0.124 AC XY: 26424 AN XY: 213002

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

African (AFR) AF: 0.0443 AC: 474 AN: 10692

American (AMR) AF: 0.107 AC: 917 AN: 8534

Ashkenazi Jewish (ASJ) AF: 0.153 AC: 1415 AN: 9272

East Asian (EAS) AF: 0.233 AC: 4323 AN: 18546

South Asian (SAS) AF: 0.122 AC: 3059 AN: 25020

European-Finnish (FIN) AF: 0.144 AC: 3698 AN: 25710

Middle Eastern (MID) AF: 0.107 AC: 169 AN: 1582

European-Non Finnish (NFE) AF: 0.116 AC: 35031 AN: 302452

Other (OTH) AF: 0.125 AC: 2556 AN: 20520

⚠️ 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: 0.0758 AC: 3129 AN: 41286 Hom.: 52 Cov.: 23 AF XY: 0.0789 AC XY: 1538 AN XY: 19502

African (AFR) AF: 0.0151 AC: 154 AN: 10194

American (AMR) AF: 0.0413 AC: 116 AN: 2810

Ashkenazi Jewish (ASJ) AF: 0.206 AC: 229 AN: 1114

East Asian (EAS) AF: 0.204 AC: 396 AN: 1938

South Asian (SAS) AF: 0.0267 AC: 34 AN: 1274

European-Finnish (FIN) AF: 0.146 AC: 324 AN: 2224

Middle Eastern (MID) AF: 0.118 AC: 4 AN: 34

European-Non Finnish (NFE) AF: 0.0878 AC: 1834 AN: 20894

Other (OTH) AF: 0.0620 AC: 33 AN: 532

Alfa AF: 0.00 Hom.: 2

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.031
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; COSMIC: COSV56560533;