chrX-150614586-C-A

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

Scores

2
Splicing: ADA: 0.9109
2

Clinical Significance

Pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 1.74

Publications

0 publications found
Variant links:
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 myopathy
    Inheritance: XL Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: G2P, Ambry Genetics, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), ClinGen, Myriad Women’s Health, Orphanet

Genome browser will be placed here

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
MTM1NM_000252.3 linkc.232-3C>A splice_region_variant, intron_variant Intron 4 of 14 ENST00000370396.7 NP_000243.1 Q13496-1A0A024RC06

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MTM1ENST00000370396.7 linkc.232-3C>A splice_region_variant, intron_variant Intron 4 of 14 1 NM_000252.3 ENSP00000359423.3 Q13496-1

Frequencies

GnomAD3 genomes
Cov.:
23
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
9.92e-7
AC:
1
AN:
1007845
Hom.:
0
Cov.:
20
AF XY:
0.00
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:
0.00
AC:
0
AN:
24664
American (AMR)
AF:
0.00
AC:
0
AN:
34863
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
18681
East Asian (EAS)
AF:
0.00
AC:
0
AN:
29623
South Asian (SAS)
AF:
0.00
AC:
0
AN:
51603
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
40159
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
3958
European-Non Finnish (NFE)
AF:
0.00000131
AC:
1
AN:
761185
Other (OTH)
AF:
0.00
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
Alfa
AF:
0.00
Hom.:
0

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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.40
CADD
Benign
18
DANN
Benign
0.77
PhyloP100
1.7
Mutation Taster
=14/86
disease causing (ClinVar)

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.91
dbscSNV1_RF
Benign
0.62
SpliceAI score (max)
0.47
Details are displayed if max score is > 0.2
DS_AL_spliceai
0.47
Position offset: 3

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

Publications

Other links and lift over

dbSNP: rs587783814; hg19: chrX-149783059; API