Variant chr22-27750998-C-CCTTGGCGTCA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PVS1_StrongPM2PP5

The NM_002430.3(MN1):c.3879_3880insTGACGCCAAG(p.Ala1294Ter) variant causes a stop gained, frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (no stars).

Frequency

Genomes: not found (cov: 32)

Consequence

MN1
NM_002430.3 stop_gained, frameshift

Scores

Not classified

Clinical Significance

Pathogenic/Likely pathogenic no assertion criteria provided P:2

Conservation

PhyloP100: 4.14

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

PVS1

Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. There are 4 pathogenic variants in the truncated region.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 22-27750998-C-CCTTGGCGTCA is Pathogenic according to our data. Variant chr22-27750998-C-CCTTGGCGTCA is described in ClinVar as [Likely_pathogenic]. Clinvar id is 812561.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MN1	NM_002430.3 linkuse as main transcript	c.3879_3880insTGACGCCAAG	p.Ala1294Ter	stop_gained, frameshift_variant	2/2	ENST00000302326.5	NP_002421.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
MN1	ENST00000302326.5 linkuse as main transcript	c.3879_3880insTGACGCCAAG	p.Ala1294Ter	stop_gained, frameshift_variant	2/2	1	NM_002430.3	ENSP00000304956	P1
MN1	ENST00000497225.1 linkuse as main transcript	n.235_236insTGACGCCAAG		non_coding_transcript_exon_variant	2/2	1
MN1	ENST00000703102.1 linkuse as main transcript	n.404_405insTGACGCCAAG		non_coding_transcript_exon_variant	2/2
MN1	ENST00000424656.1 linkuse as main transcript	c.232_233insTGACGCCAAG	p.Ala79Ter	stop_gained, frameshift_variant, NMD_transcript_variant	2/3	5		ENSP00000397805

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Significance: Pathogenic/Likely pathogenic

Submissions summary: Pathogenic:2

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

MN1 C-terminal truncation (MCTT) syndrome

Pathogenic:1

Likely pathogenic, no assertion criteria provided

research

University of Washington Center for Mendelian Genomics, University of Washington

- -

CEBALID syndrome

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Feb 14, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over