rs587783790
Variant summary
Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7
The NM_000252.3(MTM1):c.141A>G(p.Lys47Lys) variant causes a synonymous 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. Variant has been reported in ClinVar as Uncertain significance (★). The gene MTM1 is included in the ClinGen Criteria Specification Registry.
Frequency
Genomes: not found (cov: 23)
Exomes 𝑓: 9.5e-7 ( 0 hom. 0 hem. )
Failed GnomAD Quality Control
Consequence
MTM1
NM_000252.3 synonymous
NM_000252.3 synonymous
Scores
3
Clinical Significance
Conservation
PhyloP100: 2.22
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: ClinGen, G2P, Orphanet, Genomics England PanelApp, Myriad Women's Health, Labcorp Genetics (formerly Invitae), Ambry Genetics
Genome browser will be placed here
new If you want to explore the variant's impact on the transcript NM_000252.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.
ACMG classification
Specifications for MTM1 are available in the ClinGen Criteria Specification Registry and recommended for reference when assigning criteria.
Classification was made for transcript
Our verdict: Likely_benign. The variant received -3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.48).
BP7
Synonymous conserved (PhyloP=2.22 with no splicing effect.
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.141A>G | p.Lys47Lys | synonymous | Exon 4 of 15 | NP_000243.1 | Q13496-1 | ||
| MTM1 | c.141A>G | p.Lys47Lys | synonymous | Exon 4 of 15 | NP_001363837.1 | Q13496-1 | |||
| MTM1 | c.141A>G | p.Lys47Lys | synonymous | Exon 4 of 15 | NP_001363835.1 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| MTM1 | TSL:1 MANE Select | c.141A>G | p.Lys47Lys | synonymous | Exon 4 of 15 | ENSP00000359423.3 | Q13496-1 | ||
| MTM1 | c.141A>G | p.Lys47Lys | synonymous | Exon 4 of 16 | ENSP00000510607.1 | A0A8I5KZ76 | |||
| MTM1 | c.141A>G | p.Lys47Lys | synonymous | Exon 4 of 16 | ENSP00000536517.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
23
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 9.52e-7 AC: 1AN: 1050462Hom.: 0 Cov.: 21 AF XY: 0.00 AC XY: 0AN XY: 326698 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:
1050462
Hom.:
Cov.:
21
AF XY:
AC XY:
0
AN XY:
326698
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:
25497
American (AMR)
AF:
AC:
0
AN:
34911
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
19007
East Asian (EAS)
AF:
AC:
0
AN:
29901
South Asian (SAS)
AF:
AC:
0
AN:
52767
European-Finnish (FIN)
AF:
AC:
0
AN:
40440
Middle Eastern (MID)
AF:
AC:
0
AN:
3806
European-Non Finnish (NFE)
AF:
AC:
1
AN:
799702
Other (OTH)
AF:
AC:
0
AN:
44431
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), 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
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>80
Age
GnomAD4 genome
GnomAD4 genome
Cov.:
23
ClinVar
ClinVar submissions
View on ClinVar Significance:Uncertain significance
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
-
1
-
Severe X-linked myotubular myopathy (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
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
MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.
Publications
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