NM_006554.5:c.295_296delCT
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_006554.5(MTX2):c.295_296delCT(p.Leu99fs) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000142 in 1,410,568 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
MTX2
NM_006554.5 frameshift
NM_006554.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 8.01
Publications
2 publications found
Genes affected
MTX2 (HGNC:7506): (metaxin 2) The protein encoded by this gene is highly similar to the metaxin 2 protein from mouse, which has been shown to interact with the mitochondrial membrane protein metaxin 1. Because of this similarity, it is thought that the encoded protein is peripherally associated with the cytosolic face of the outer mitochondrial membrane, and that it is involved in the import of proteins into the mitochondrion. Alternative splicing results in multiple transcript variants. A related pseudogene has been identified on chromosome 7. [provided by RefSeq, Jun 2009]
MTX2 Gene-Disease associations (from GenCC):
- mandibuloacral dysplasia progeroid syndromeInheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen
- mandibuloacral dysplasiaInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 11 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 2-176328298-TTC-T is Pathogenic according to our data. Variant chr2-176328298-TTC-T is described in ClinVar as Pathogenic. ClinVar VariationId is 827676.Status of the report is no_assertion_criteria_provided, 0 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_006554.5. 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 |
|---|---|---|---|---|---|---|---|---|---|
| MTX2 | NM_006554.5 | MANE Select | c.295_296delCT | p.Leu99fs | frameshift | Exon 6 of 10 | NP_006545.1 | O75431-1 | |
| MTX2 | NM_001006635.3 | c.265_266delCT | p.Leu89fs | frameshift | Exon 7 of 11 | NP_001006636.1 | O75431-2 | ||
| MTX2 | NM_001319097.2 | c.295_296delCT | p.Leu99fs | frameshift | Exon 6 of 10 | NP_001306026.1 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| MTX2 | ENST00000249442.11 | TSL:1 MANE Select | c.295_296delCT | p.Leu99fs | frameshift | Exon 6 of 10 | ENSP00000249442.6 | O75431-1 | |
| MTX2 | ENST00000420864.5 | TSL:1 | n.*385_*386delCT | non_coding_transcript_exon | Exon 7 of 11 | ENSP00000403545.1 | F8WCW1 | ||
| MTX2 | ENST00000420864.5 | TSL:1 | n.*385_*386delCT | 3_prime_UTR | Exon 7 of 11 | ENSP00000403545.1 | F8WCW1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
31
GnomAD2 exomes AF: 0.00000458 AC: 1AN: 218512 AF XY: 0.00000839 show subpopulations
GnomAD2 exomes
AF:
AC:
1
AN:
218512
AF XY:
Gnomad AFR exome
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Gnomad AMR exome
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Gnomad ASJ exome
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Gnomad EAS exome
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Gnomad FIN exome
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Gnomad NFE exome
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Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000142 AC: 2AN: 1410568Hom.: 0 AF XY: 0.00000143 AC XY: 1AN XY: 701674 show subpopulations
GnomAD4 exome
AF:
AC:
2
AN:
1410568
Hom.:
AF XY:
AC XY:
1
AN XY:
701674
show subpopulations
African (AFR)
AF:
AC:
0
AN:
30768
American (AMR)
AF:
AC:
0
AN:
34560
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
24064
East Asian (EAS)
AF:
AC:
0
AN:
38226
South Asian (SAS)
AF:
AC:
0
AN:
76754
European-Finnish (FIN)
AF:
AC:
0
AN:
52220
Middle Eastern (MID)
AF:
AC:
0
AN:
5414
European-Non Finnish (NFE)
AF:
AC:
2
AN:
1090816
Other (OTH)
AF:
AC:
0
AN:
57746
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
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Allele balance
Age Distribution
Exome Het
Variant carriers
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GnomAD4 genome
GnomAD4 genome
Cov.:
31
ClinVar
ClinVar submissions
View on ClinVar Significance:Pathogenic
Revision:no assertion criteria provided
Pathogenic
VUS
Benign
Condition
1
-
-
Hypertensive disorder;C0025990:Micrognathia;C0040433:Dental crowding;C1260926:Abnormality of skin pigmentation;C1857710:Progeroid facial appearance;C1859778:Postnatal growth retardation;C4021159:Facial shape deformation;C4025739:Acroosteolysis of distal phalanges (feet);C4025870:Abnormal mandible morphology;C4025901:Abnormality of body height (1)
1
-
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Mandibuloacral dysplasia progeroid syndrome (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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