Variant chr22-27751043-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_StrongPM2PP5_Moderate

The ENST00000302326.5(MN1):c.3835C>T(p.Gln1279Ter) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MN1
ENST00000302326.5 stop_gained

Scores

Clinical Significance

Pathogenic criteria provided, single submitter P:2

Conservation

PhyloP100: 9.06

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 8 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 13 pathogenic variants in the truncated region.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 22-27751043-G-A is Pathogenic according to our data. Variant chr22-27751043-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 812563.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr22-27751043-G-A is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MN1	NM_002430.3 linkuse as main transcript	c.3835C>T	p.Gln1279Ter	stop_gained	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.3835C>T	p.Gln1279Ter	stop_gained	2/2	1	NM_002430.3	ENSP00000304956	P1
MN1	ENST00000497225.1 linkuse as main transcript	n.191C>T		non_coding_transcript_exon_variant	2/2	1
MN1	ENST00000703102.1 linkuse as main transcript	n.360C>T		non_coding_transcript_exon_variant	2/2
MN1	ENST00000424656.1 linkuse as main transcript	c.190C>T	p.Gln64Ter	stop_gained, NMD_transcript_variant	2/3	5		ENSP00000397805

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1449244

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

719168

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

CEBALID syndrome

Pathogenic:2

Pathogenic, criteria provided, single submitter	curation	SIB Swiss Institute of Bioinformatics	Jul 29, 2020	This variant is interpreted as Pathogenic for CEBALID syndrome, autosomal dominant. The following ACMG Tag(s) were applied: Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium (PM2); Located in a mutational hot spot and/or critical and well-established functional domain (e.g., active site of an enzyme) without benign variation (PM1); Protein length changes as a result of in-frame deletions/insertions in a nonrepeat region or stop-loss variants (PM4); De novo (paternity and maternity confirmed) (PS2). -
Pathogenic, no assertion criteria provided	literature only	OMIM	Feb 14, 2020	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.62

BayesDel_noAF

Pathogenic

0.65

CADD

Pathogenic

DANN

Uncertain

1.0

Eigen

Pathogenic

1.1

Eigen_PC

Pathogenic

0.93

FATHMM_MKL

Pathogenic

0.99

MutationTaster

Benign

1.0

Vest4

0.81

GERP RS

4.1

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

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