Genetic Variant NM_002430.3:c.*131_*133dupTTT (chr22-27750781-G-GAAA) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_002430.3(MN1):c.*131_*133dupTTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000121 in 497,820 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), which may indicate mosaicism or somatic mutations in the reference population data. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000024 ( 0 hom., cov: 23)

Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

MN1
NM_002430.3 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0310

Publications

0 publications found

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 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

MN1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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.131_133dupTTT		3_prime_UTR	Exon 2 of 2	NP_002421.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MN1	ENST00000302326.5	TSL:1 MANE Select	c.131_133dupTTT	3_prime_UTR	Exon 2 of 2	ENSP00000304956.4	Q10571
MN1	ENST00000497225.1	TSL:1	n.450_452dupTTT	non_coding_transcript_exon	Exon 2 of 2
MN1	ENST00000424656.1	TSL:5	n.131_133dupTTT	non_coding_transcript_exon	Exon 2 of 3	ENSP00000397805.1	H7C105

Frequencies

GnomAD3 genomes

AF:

0.0000241

AC:

AN:

41416

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000446

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000129

AC:

AN:

456404

Hom.:

Cov.:

AF XY:

0.000130

AC XY:

AN XY:

230036

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

11264

American (AMR)

AF:

0.000212

AC:

AN:

9436

Ashkenazi Jewish (ASJ)

AF:

0.000194

AC:

AN:

10332

East Asian (EAS)

AF:

0.000315

AC:

AN:

22254

South Asian (SAS)

AF:

0.000154

AC:

AN:

26002

European-Finnish (FIN)

AF:

0.000143

AC:

AN:

28048

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1716

European-Non Finnish (NFE)

AF:

0.000117

AC:

AN:

324850

Other (OTH)

AF:

0.0000889

AC:

AN:

22502

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.259

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000241

AC:

AN:

41416

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

19570

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

10162

American (AMR)

AF:

0.00

AC:

AN:

2822

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1120

East Asian (EAS)

AF:

0.00

AC:

AN:

1940

South Asian (SAS)

AF:

0.00

AC:

AN:

1282

European-Finnish (FIN)

AF:

0.000446

AC:

AN:

2242

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

21006

Other (OTH)

AF:

0.00

AC:

AN:

532

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.031

Splicing

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

Publications

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NM_002430.3:c.131_133dupTTT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over