22-27750929-C-T

Variant names:

• chr22-27750929-C-T
• NM_002430.3:c.3949G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_002430.3(MN1):​c.3949G>A​(p.Ala1317Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MN1 NM_002430.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.09
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.3949G>A	p.Ala1317Thr	missense	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.3949G>A	p.Ala1317Thr	missense	Exon 2 of 2	ENSP00000304956.4	Q10571
	MN1	ENST00000497225.1	TSL:1	n.305G>A		non_coding_transcript_exon	Exon 2 of 2
	MN1	ENST00000424656.1	TSL:5	n.301G>A		non_coding_transcript_exon	Exon 2 of 3	ENSP00000397805.1	H7C105

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1445360 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 717078

African (AFR) AF: 0.00 AC: 0 AN: 33100

American (AMR) AF: 0.00 AC: 0 AN: 43124

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25358

East Asian (EAS) AF: 0.00 AC: 0 AN: 39120

South Asian (SAS) AF: 0.00 AC: 0 AN: 83828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53030

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5718

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1102440

Other (OTH) AF: 0.00 AC: 0 AN: 59642

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.94
BayesDel_addAF	Uncertain	0.022	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.20	T
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.055	D
MetaRNN	Uncertain	0.52	D
MetaSVM	Benign	-0.59	T
MutationAssessor	Benign	0.34	N
PhyloP100		7.1
PrimateAI	Pathogenic	0.80	T
PROVEAN	Uncertain	-2.7	D
REVEL	Uncertain	0.32
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.50
MutPred		0.38		Gain of relative solvent accessibility (P = 0.09)
MVP		0.95
ClinPred		0.98	D
GERP RS		4.1
Varity_R		0.58
gMVP		0.35
Mutation Taster		=59/41	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

hg19: chr22-28146917;