rs587783814
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM2PP5_ModerateBP4
The NM_000252.3(MTM1):c.232-3C>A variant causes a splice region, splice polypyrimidine tract, 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, splice_polypyrimidine_tract, intron
NM_000252.3 splice_region, splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.9109
2
Clinical Significance
Conservation
PhyloP100: 1.74
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 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 ClinVar 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 Lovd as [Pathogenic].
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/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MTM1 | NM_000252.3 | c.232-3C>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000370396.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MTM1 | ENST00000370396.7 | c.232-3C>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_000252.3 | P1 |
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
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
Gnomad4 AFR exome
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GnomAD4 genome ? Cov.: 23
GnomAD4 genome
?
Cov.:
23
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Severe X-linked myotubular myopathy Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Feb 08, 2013 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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