22-27751043-G-A
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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
ENST00000302326.5 stop_gained
Scores
5
1
1
Clinical Significance
Conservation
PhyloP100: 9.06
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]
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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 | 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 | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MN1 | ENST00000302326.5 | c.3835C>T | p.Gln1279Ter | stop_gained | 2/2 | 1 | NM_002430.3 | ENSP00000304956 | P1 | |
MN1 | ENST00000497225.1 | n.191C>T | non_coding_transcript_exon_variant | 2/2 | 1 | |||||
MN1 | ENST00000703102.1 | n.360C>T | non_coding_transcript_exon_variant | 2/2 | ||||||
MN1 | ENST00000424656.1 | c.190C>T | p.Gln64Ter | stop_gained, NMD_transcript_variant | 2/3 | 5 | ENSP00000397805 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1449244Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 719168
GnomAD4 exome
Data not reliable, filtered out with message: AC0
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0
AN:
1449244
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Cov.:
31
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0
AN XY:
719168
Gnomad4 AFR exome
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GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
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:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
MutationTaster
Benign
D
Vest4
GERP RS
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at