X-150641290-A-T

Variant names:

• chrX-150641290-A-T
• rs587783835
• NM_000252.3:c.550A>T

Variant summary

Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The NM_000252.3(MTM1):​c.550A>T​(p.Arg184*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 22)
• Consequence: MTM1 NM_000252.3 stop_gained
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 2.92
• 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 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

ACMG classification

Our verdict: Pathogenic. The variant received 12 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant X-150641290-A-T is Pathogenic according to our data. Variant chrX-150641290-A-T is described in CliVar as Likely_pathogenic. Clinvar id is 1724890.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150641290-A-T is described in CliVar as Likely_pathogenic. Clinvar id is 1724890.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150641290-A-T is described in CliVar as Likely_pathogenic. Clinvar id is 1724890.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150641290-A-T is described in CliVar as Likely_pathogenic. Clinvar id is 1724890.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150641290-A-T is described in CliVar as Likely_pathogenic. Clinvar id is 1724890.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150641290-A-T is described in CliVar as Likely_pathogenic. Clinvar id is 1724890.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150641290-A-T is described in CliVar as Likely_pathogenic. Clinvar id is 1724890.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150641290-A-T is described in CliVar as Likely_pathogenic. Clinvar id is 1724890.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150641290-A-T is described in CliVar as Likely_pathogenic. Clinvar id is 1724890.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150641290-A-T is described in CliVar as Likely_pathogenic. Clinvar id is 1724890.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150641290-A-T is described in CliVar as Likely_pathogenic. Clinvar id is 1724890.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150641290-A-T is described in CliVar as Likely_pathogenic. Clinvar id is 1724890.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150641290-A-T is described in CliVar as Likely_pathogenic. Clinvar id is 1724890.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150641290-A-T is described in CliVar as Likely_pathogenic. Clinvar id is 1724890.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150641290-A-T is described in CliVar as Likely_pathogenic. Clinvar id is 1724890.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150641290-A-T is described in CliVar as Likely_pathogenic. Clinvar id is 1724890.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150641290-A-T is described in CliVar as Likely_pathogenic. Clinvar id is 1724890.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150641290-A-T is described in CliVar as Likely_pathogenic. Clinvar id is 1724890.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150641290-A-T is described in CliVar as Likely_pathogenic. Clinvar id is 1724890.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150641290-A-T is described in CliVar as Likely_pathogenic. Clinvar id is 1724890.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150641290-A-T is described in CliVar as Likely_pathogenic. Clinvar id is 1724890.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150641290-A-T is described in CliVar as Likely_pathogenic. Clinvar id is 1724890.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150641290-A-T is described in CliVar as Likely_pathogenic. Clinvar id is 1724890.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150641290-A-T is described in CliVar as Likely_pathogenic. Clinvar id is 1724890.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150641290-A-T is described in CliVar as Likely_pathogenic. Clinvar id is 1724890.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150641290-A-T is described in CliVar as Likely_pathogenic. Clinvar id is 1724890.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150641290-A-T is described in CliVar as Likely_pathogenic. Clinvar id is 1724890.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150641290-A-T is described in CliVar as Likely_pathogenic. Clinvar id is 1724890.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150641290-A-T is described in CliVar as Likely_pathogenic. Clinvar id is 1724890.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150641290-A-T is described in CliVar as Likely_pathogenic. Clinvar id is 1724890.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150641290-A-T is described in CliVar as Likely_pathogenic. Clinvar id is 1724890.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150641290-A-T is described in CliVar as Likely_pathogenic. Clinvar id is 1724890.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150641290-A-T is described in CliVar as Likely_pathogenic. Clinvar id is 1724890.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150641290-A-T is described in CliVar as Likely_pathogenic. Clinvar id is 1724890.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150641290-A-T is described in CliVar as Likely_pathogenic. Clinvar id is 1724890.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150641290-A-T is described in CliVar as Likely_pathogenic. Clinvar id is 1724890.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150641290-A-T is described in CliVar as Likely_pathogenic. Clinvar id is 1724890.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150641290-A-T is described in CliVar as Likely_pathogenic. Clinvar id is 1724890.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150641290-A-T is described in CliVar as Likely_pathogenic. Clinvar id is 1724890.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150641290-A-T is described in CliVar as Likely_pathogenic. Clinvar id is 1724890.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150641290-A-T is described in CliVar as Likely_pathogenic. Clinvar id is 1724890.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150641290-A-T is described in CliVar as Likely_pathogenic. Clinvar id is 1724890.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150641290-A-T is described in CliVar as Likely_pathogenic. Clinvar id is 1724890.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150641290-A-T is described in CliVar as Likely_pathogenic. Clinvar id is 1724890.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150641290-A-T is described in CliVar as Likely_pathogenic. Clinvar id is 1724890.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150641290-A-T is described in CliVar as Likely_pathogenic. Clinvar id is 1724890.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTM1	NM_000252.3	c.550A>T	p.Arg184*	stop_gained	Exon 8 of 15	ENST00000370396.7	NP_000243.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTM1	ENST00000370396.7	c.550A>T	p.Arg184*	stop_gained	Exon 8 of 15	1	NM_000252.3	ENSP00000359423.3

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 22

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Severe X-linked myotubular myopathy Pathogenic:1

Mar 02, 2022

Myriad Genetics, Inc.

Significance: Likely pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

NM_000252.2(MTM1):c.550A>T(R184*) is expected to be pathogenic in the context of X-linked myotubular myopathy. This variant is predicted to lead to an abnormal or absent protein product due to the creation of a premature termination codon in MTM1, a gene where loss-of-function variants are known to be pathogenic. Please note: this variant was assessed in the context of healthy population screening. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.74	D
BayesDel_noAF	Pathogenic	0.60
CADD	Pathogenic	36
DANN	Uncertain	1.0
FATHMM_MKL	Uncertain	0.95	D
PhyloP100		2.9
Vest4		0.95
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=0/200	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs587783835; hg19: chrX-149809763;