chrX-150614586-C-A
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 3 ACMG points: 4P and 1B. PM2PP5_ModerateBP4
The NM_000252.3(MTM1):c.232-3C>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Genomes: not found (cov: 23)
Exomes 𝑓: 9.9e-7 ( 0 hom. 0 hem. )
Failed GnomAD Quality Control
Consequence
MTM1
NM_000252.3 splice_region, intron
NM_000252.3 splice_region, intron
Scores
2
Splicing: ADA: 0.9109
2
Clinical Significance
Conservation
PhyloP100: 1.74
Publications
0 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: G2P, Ambry Genetics, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), ClinGen, Myriad Women’s Health, Orphanet
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ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant X-150614586-C-A is Pathogenic according to our data. Variant chrX-150614586-C-A is described in CliVar as Pathogenic. Clinvar id is 158960.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150614586-C-A is described in CliVar as Pathogenic. Clinvar id is 158960.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150614586-C-A is described in CliVar as Pathogenic. Clinvar id is 158960.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150614586-C-A is described in CliVar as Pathogenic. Clinvar id is 158960.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150614586-C-A is described in CliVar as Pathogenic. Clinvar id is 158960.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150614586-C-A is described in CliVar as Pathogenic. Clinvar id is 158960.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150614586-C-A is described in CliVar as Pathogenic. Clinvar id is 158960.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150614586-C-A is described in CliVar as Pathogenic. Clinvar id is 158960.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150614586-C-A is described in CliVar as Pathogenic. Clinvar id is 158960.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150614586-C-A is described in CliVar as Pathogenic. Clinvar id is 158960.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150614586-C-A is described in CliVar as Pathogenic. Clinvar id is 158960.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150614586-C-A is described in CliVar as Pathogenic. Clinvar id is 158960.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150614586-C-A is described in CliVar as Pathogenic. Clinvar id is 158960.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150614586-C-A is described in CliVar as Pathogenic. Clinvar id is 158960.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150614586-C-A is described in CliVar as Pathogenic. Clinvar id is 158960.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150614586-C-A is described in CliVar as Pathogenic. Clinvar id is 158960.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150614586-C-A is described in CliVar as Pathogenic. Clinvar id is 158960.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150614586-C-A is described in CliVar as Pathogenic. Clinvar id is 158960.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150614586-C-A is described in CliVar as Pathogenic. Clinvar id is 158960.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150614586-C-A is described in CliVar as Pathogenic. Clinvar id is 158960.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150614586-C-A is described in CliVar as Pathogenic. Clinvar id is 158960.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150614586-C-A is described in CliVar as Pathogenic. Clinvar id is 158960.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150614586-C-A is described in CliVar as Pathogenic. Clinvar id is 158960.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150614586-C-A is described in CliVar as Pathogenic. Clinvar id is 158960.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150614586-C-A is described in CliVar as Pathogenic. Clinvar id is 158960.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150614586-C-A is described in CliVar as Pathogenic. Clinvar id is 158960.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150614586-C-A is described in CliVar as Pathogenic. Clinvar id is 158960.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150614586-C-A is described in CliVar as Pathogenic. Clinvar id is 158960.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150614586-C-A is described in CliVar as Pathogenic. Clinvar id is 158960.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150614586-C-A is described in CliVar as Pathogenic. Clinvar id is 158960.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150614586-C-A is described in CliVar as Pathogenic. Clinvar id is 158960.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150614586-C-A is described in CliVar as Pathogenic. Clinvar id is 158960.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150614586-C-A is described in CliVar as Pathogenic. Clinvar id is 158960.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150614586-C-A is described in CliVar as Pathogenic. Clinvar id is 158960.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150614586-C-A is described in CliVar as Pathogenic. Clinvar id is 158960.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150614586-C-A is described in CliVar as Pathogenic. Clinvar id is 158960.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150614586-C-A is described in CliVar as Pathogenic. Clinvar id is 158960.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150614586-C-A is described in CliVar as Pathogenic. Clinvar id is 158960.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150614586-C-A is described in CliVar as Pathogenic. Clinvar id is 158960.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150614586-C-A is described in CliVar as Pathogenic. Clinvar id is 158960.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150614586-C-A is described in CliVar as Pathogenic. Clinvar id is 158960.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150614586-C-A is described in CliVar as Pathogenic. Clinvar id is 158960.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150614586-C-A is described in CliVar as Pathogenic. Clinvar id is 158960.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150614586-C-A is described in CliVar as Pathogenic. Clinvar id is 158960.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150614586-C-A is described in CliVar as Pathogenic. Clinvar id is 158960.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150614586-C-A is described in CliVar as Pathogenic. Clinvar id is 158960.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150614586-C-A is described in CliVar as Pathogenic. Clinvar id is 158960.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150614586-C-A is described in CliVar as Pathogenic. Clinvar id is 158960.Status of the report is criteria_provided_single_submitter, 1 stars.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.4). . Strength limited to SUPPORTING due to the PP5.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MTM1 | NM_000252.3 | c.232-3C>A | splice_region_variant, intron_variant | Intron 4 of 14 | ENST00000370396.7 | NP_000243.1 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 23
GnomAD3 genomes
Cov.:
23
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 9.92e-7 AC: 1AN: 1007845Hom.: 0 Cov.: 20 AF XY: 0.00 AC XY: 0AN XY: 302171 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
AC:
1
AN:
1007845
Hom.:
Cov.:
20
AF XY:
AC XY:
0
AN XY:
302171
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
24664
American (AMR)
AF:
AC:
0
AN:
34863
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
18681
East Asian (EAS)
AF:
AC:
0
AN:
29623
South Asian (SAS)
AF:
AC:
0
AN:
51603
European-Finnish (FIN)
AF:
AC:
0
AN:
40159
Middle Eastern (MID)
AF:
AC:
0
AN:
3958
European-Non Finnish (NFE)
AF:
AC:
1
AN:
761185
Other (OTH)
AF:
AC:
0
AN:
43109
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), 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
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
6
8
10
<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 Cov.: 23
GnomAD4 genome
Cov.:
23
Alfa
AF:
Hom.:
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Severe X-linked myotubular myopathy Pathogenic:1
Feb 08, 2013
Genetic Services Laboratory, University of Chicago
Significance:Pathogenic
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AL_spliceai
Position offset: 3
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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