chrX-150649902-G-A

Variant names:

• chrX-150649902-G-A
• rs587783751
• NM_000252.3:c.1053+1G>A

Variant summary

Our verdict is Likely pathogenic. The variant received 7 ACMG points: 7P and 0B. PVS1_Strong PM2 PP5

The NM_000252.3(MTM1):​c.1053+1G>A variant causes a splice donor, intron change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 1/1 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 23)
• Consequence: MTM1 NM_000252.3 splice_donor, intron
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 9.63
• 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: Likely_pathogenic. The variant received 7 ACMG points.

• PVS1: Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.102649 fraction of the gene. No cryptic splice site detected. Exon removal is inframe change.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant X-150649902-G-A is Pathogenic according to our data. Variant chrX-150649902-G-A is described in CliVar as Pathogenic. Clinvar id is 633472.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-150649902-G-A is described in CliVar as Pathogenic. Clinvar id is 633472.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-150649902-G-A is described in CliVar as Pathogenic. Clinvar id is 633472.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-150649902-G-A is described in CliVar as Pathogenic. Clinvar id is 633472.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-150649902-G-A is described in CliVar as Pathogenic. Clinvar id is 633472.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-150649902-G-A is described in CliVar as Pathogenic. Clinvar id is 633472.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-150649902-G-A is described in CliVar as Pathogenic. Clinvar id is 633472.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-150649902-G-A is described in CliVar as Pathogenic. Clinvar id is 633472.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-150649902-G-A is described in CliVar as Pathogenic. Clinvar id is 633472.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-150649902-G-A is described in CliVar as Pathogenic. Clinvar id is 633472.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-150649902-G-A is described in CliVar as Pathogenic. Clinvar id is 633472.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-150649902-G-A is described in CliVar as Pathogenic. Clinvar id is 633472.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-150649902-G-A is described in CliVar as Pathogenic. Clinvar id is 633472.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-150649902-G-A is described in CliVar as Pathogenic. Clinvar id is 633472.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-150649902-G-A is described in CliVar as Pathogenic. Clinvar id is 633472.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-150649902-G-A is described in CliVar as Pathogenic. Clinvar id is 633472.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-150649902-G-A is described in CliVar as Pathogenic. Clinvar id is 633472.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-150649902-G-A is described in CliVar as Pathogenic. Clinvar id is 633472.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-150649902-G-A is described in CliVar as Pathogenic. Clinvar id is 633472.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-150649902-G-A is described in CliVar as Pathogenic. Clinvar id is 633472.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-150649902-G-A is described in CliVar as Pathogenic. Clinvar id is 633472.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-150649902-G-A is described in CliVar as Pathogenic. Clinvar id is 633472.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-150649902-G-A is described in CliVar as Pathogenic. Clinvar id is 633472.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-150649902-G-A is described in CliVar as Pathogenic. Clinvar id is 633472.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-150649902-G-A is described in CliVar as Pathogenic. Clinvar id is 633472.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-150649902-G-A is described in CliVar as Pathogenic. Clinvar id is 633472.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-150649902-G-A is described in CliVar as Pathogenic. Clinvar id is 633472.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-150649902-G-A is described in CliVar as Pathogenic. Clinvar id is 633472.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-150649902-G-A is described in CliVar as Pathogenic. Clinvar id is 633472.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-150649902-G-A is described in CliVar as Pathogenic. Clinvar id is 633472.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-150649902-G-A is described in CliVar as Pathogenic. Clinvar id is 633472.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-150649902-G-A is described in CliVar as Pathogenic. Clinvar id is 633472.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-150649902-G-A is described in CliVar as Pathogenic. Clinvar id is 633472.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-150649902-G-A is described in CliVar as Pathogenic. Clinvar id is 633472.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-150649902-G-A is described in CliVar as Pathogenic. Clinvar id is 633472.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-150649902-G-A is described in CliVar as Pathogenic. Clinvar id is 633472.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-150649902-G-A is described in CliVar as Pathogenic. Clinvar id is 633472.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-150649902-G-A is described in CliVar as Pathogenic. Clinvar id is 633472.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-150649902-G-A is described in CliVar as Pathogenic. Clinvar id is 633472.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-150649902-G-A is described in CliVar as Pathogenic. Clinvar id is 633472.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-150649902-G-A is described in CliVar as Pathogenic. Clinvar id is 633472.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-150649902-G-A is described in CliVar as Pathogenic. Clinvar id is 633472.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-150649902-G-A is described in CliVar as Pathogenic. Clinvar id is 633472.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-150649902-G-A is described in CliVar as Pathogenic. Clinvar id is 633472.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-150649902-G-A is described in CliVar as Pathogenic. Clinvar id is 633472.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-150649902-G-A is described in CliVar as Pathogenic. Clinvar id is 633472.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-150649902-G-A is described in CliVar as Pathogenic. Clinvar id is 633472.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-150649902-G-A is described in CliVar as Pathogenic. Clinvar id is 633472.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTM1	NM_000252.3	c.1053+1G>A		splice_donor_variant, intron_variant	Intron 10 of 14	ENST00000370396.7	NP_000243.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTM1	ENST00000370396.7	c.1053+1G>A		splice_donor_variant, intron_variant	Intron 10 of 14	1	NM_000252.3	ENSP00000359423.3

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 23

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Severe X-linked myotubular myopathy Pathogenic:1

Nov 29, 2007

Clinical Molecular Genetics Laboratory, Johns Hopkins All Children's Hospital

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.74	D
BayesDel_noAF	Pathogenic	0.41
CADD	Pathogenic	32
DANN	Uncertain	1.0
FATHMM_MKL	Pathogenic	1.0	D
PhyloP100		9.6
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=0/100	disease causing (ClinVar)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.99		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.22		Position offset: -17
DS_DL_spliceai		0.99		Position offset: -1

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

Other links and lift over

dbSNP: rs587783751; hg19: chrX-149818375;