NM_002430.3:c.3849_3850delCCinsA

Variant names:

• chr22-27751028-GG-T
• rs1932759453
• NM_002430.3:c.3849_3850delCCinsA

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1_Strong PS1 PM2 PP5

The NM_002430.3(MN1):​c.3849_3850delCCinsA​(p.His1284ThrfsTer36) variant causes a frameshift, missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (no stars). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Pathogenic in Lovd.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MN1 NM_002430.3 frameshift, missense
• Clinical Significance: Likely pathogenic no assertion criteria provided P:1
• 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]

ACMG classification

Verdict is Pathogenic. Variant got 11 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 5 pathogenic variants in the truncated region.
• PS1: Transcript NM_002430.3 (MN1) is affected with MISSENSE_VARIANT having same AA change as one Pathogenic present in Lovd
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 22-27751028-GG-T is Pathogenic according to our data. Variant chr22-27751028-GG-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 979062.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MN1	NM_002430.3	c.3849_3850delCCinsA	p.His1284ThrfsTer36	frameshift_variant, missense_variant	Exon 2 of 2	ENST00000302326.5	NP_002421.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MN1	ENST00000302326.5	c.3849_3850delCCinsA	p.His1284ThrfsTer36	frameshift_variant, missense_variant	Exon 2 of 2	1	NM_002430.3	ENSP00000304956.4
MN1	ENST00000497225.1	n.205_206delCCinsA		non_coding_transcript_exon_variant	Exon 2 of 2	1
MN1	ENST00000424656.1	n.201_202delCCinsA		non_coding_transcript_exon_variant	Exon 2 of 3	5		ENSP00000397805.1
MN1	ENST00000703102.1	n.374_375delCCinsA		non_coding_transcript_exon_variant	Exon 2 of 2

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

MN1 C-terminal truncation (MCTT) syndrome Pathogenic:1

-

University of Washington Center for Mendelian Genomics, University of Washington

Significance: Likely pathogenic

Review Status: no assertion criteria provided

Collection Method: research

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1932759453; hg19: chr22-28147016;