rs587783752
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Pathogenic. The variant received 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_000252.3(MTM1):c.1088_1089delAA(p.Lys363SerfsTer14) variant causes a frameshift change. The variant allele was found at a frequency of 0.000000911 in 1,098,148 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. Variant has been reported in ClinVar as Pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 23)
Exomes 𝑓: 9.1e-7 ( 0 hom. 0 hem. )
Consequence
MTM1
NM_000252.3 frameshift
NM_000252.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 6.16
Publications
2 publications found
Genes affected
MTM1 (HGNC:7448): (myotubularin 1) This gene encodes a dual-specificity phosphatase that acts on both phosphotyrosine and phosphoserine. It is required for muscle cell differentiation and mutations in this gene have been identified as being responsible for X-linked myotubular myopathy. [provided by RefSeq, Jul 2008]
MTM1 Gene-Disease associations (from GenCC):
- X-linked myotubular myopathyInheritance: XL Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Orphanet, ClinGen, G2P, Myriad Women’s Health, Ambry Genetics
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ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 18 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 X-150657853-CAA-C is Pathogenic according to our data. Variant chrX-150657853-CAA-C is described in ClinVar as Pathogenic. ClinVar VariationId is 158894.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_000252.3. 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 |
|---|---|---|---|---|---|---|---|---|---|
| MTM1 | MANE Select | c.1088_1089delAA | p.Lys363SerfsTer14 | frameshift | Exon 11 of 15 | NP_000243.1 | Q13496-1 | ||
| MTM1 | c.1088_1089delAA | p.Lys363SerfsTer14 | frameshift | Exon 11 of 15 | NP_001363837.1 | Q13496-1 | |||
| MTM1 | c.1088_1089delAA | p.Lys363SerfsTer14 | frameshift | Exon 11 of 15 | NP_001363835.1 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| MTM1 | TSL:1 MANE Select | c.1088_1089delAA | p.Lys363SerfsTer14 | frameshift | Exon 11 of 15 | ENSP00000359423.3 | Q13496-1 | ||
| MTM1 | c.1133_1134delAA | p.Lys378SerfsTer14 | frameshift | Exon 12 of 16 | ENSP00000510607.1 | A0A8I5KZ76 | |||
| MTM1 | c.1133_1134delAA | p.Lys378SerfsTer14 | frameshift | Exon 12 of 16 | ENSP00000536517.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
23
GnomAD4 exome AF: 9.11e-7 AC: 1AN: 1098148Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 363510 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
1098148
Hom.:
AF XY:
AC XY:
0
AN XY:
363510
show subpopulations
African (AFR)
AF:
AC:
0
AN:
26403
American (AMR)
AF:
AC:
0
AN:
35206
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
19386
East Asian (EAS)
AF:
AC:
0
AN:
30202
South Asian (SAS)
AF:
AC:
0
AN:
54149
European-Finnish (FIN)
AF:
AC:
0
AN:
40505
Middle Eastern (MID)
AF:
AC:
0
AN:
4137
European-Non Finnish (NFE)
AF:
AC:
1
AN:
842064
Other (OTH)
AF:
AC:
0
AN:
46096
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
GnomAD4 genome
Cov.:
23
ClinVar
ClinVar submissions
View on ClinVar Significance:Pathogenic
Revision:criteria provided, multiple submitters, no conflicts
Pathogenic
VUS
Benign
Condition
1
-
-
not provided (1)
1
-
-
Severe X-linked myotubular myopathy (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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