chrX-150614696-T-C
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_000252.3(MTM1):c.339T>C(p.Cys113=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000229 in 1,058,315 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 68 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0010 ( 0 hom., 36 hem., cov: 22)
Exomes 𝑓: 0.00014 ( 0 hom. 32 hem. )
Consequence
MTM1
NM_000252.3 synonymous
NM_000252.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.27
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 Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.48).
BP6
?
Variant X-150614696-T-C is Benign according to our data. Variant chrX-150614696-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 285094.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-150614696-T-C is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=2.27 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000999 (111/111129) while in subpopulation AFR AF= 0.00337 (103/30549). AF 95% confidence interval is 0.00284. There are 0 homozygotes in gnomad4. There are 36 alleles in male gnomad4 subpopulation. Median coverage is 22. This position pass quality control queck.
BS2
?
High Hemizygotes in GnomAd at 36 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MTM1 | NM_000252.3 | c.339T>C | p.Cys113= | synonymous_variant | 5/15 | ENST00000370396.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MTM1 | ENST00000370396.7 | c.339T>C | p.Cys113= | synonymous_variant | 5/15 | 1 | NM_000252.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000999 AC: 111AN: 111075Hom.: 0 Cov.: 22 AF XY: 0.00108 AC XY: 36AN XY: 33285
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GnomAD3 exomes AF: 0.000349 AC: 60AN: 171830Hom.: 0 AF XY: 0.000240 AC XY: 14AN XY: 58308
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GnomAD4 exome AF: 0.000138 AC: 131AN: 947186Hom.: 0 Cov.: 19 AF XY: 0.000123 AC XY: 32AN XY: 259486
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GnomAD4 genome ? AF: 0.000999 AC: 111AN: 111129Hom.: 0 Cov.: 22 AF XY: 0.00108 AC XY: 36AN XY: 33349
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Dec 24, 2015 | - - |
Severe X-linked myotubular myopathy Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 24, 2024 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 29, 2021 | - - |
MTM1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Nov 14, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at