NM_000252.3:c.63+3A>T

Variant names:

• chrX-150592680-A-T
• rs587783844
• NM_000252.3:c.63+3A>T

Variant summary

Our verdict is Uncertain significance. The variant received 5 ACMG points: 5P and 0B. PM2 PP3 PP5_Moderate

The NM_000252.3(MTM1):​c.63+3A>T variant causes a splice region, 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. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely pathogenic (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: MTM1 NM_000252.3 splice_region, intron
• Scores: Splicing: ADA: 0.9987
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 1.11
• 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: Uncertain_significance. The variant received 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF, max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
• PP5: Variant X-150592680-A-T is Pathogenic according to our data. Variant chrX-150592680-A-T is described in CliVar as Likely_pathogenic. Clinvar id is 158990.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150592680-A-T is described in CliVar as Likely_pathogenic. Clinvar id is 158990.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150592680-A-T is described in CliVar as Likely_pathogenic. Clinvar id is 158990.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150592680-A-T is described in CliVar as Likely_pathogenic. Clinvar id is 158990.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150592680-A-T is described in CliVar as Likely_pathogenic. Clinvar id is 158990.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150592680-A-T is described in CliVar as Likely_pathogenic. Clinvar id is 158990.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150592680-A-T is described in CliVar as Likely_pathogenic. Clinvar id is 158990.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150592680-A-T is described in CliVar as Likely_pathogenic. Clinvar id is 158990.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150592680-A-T is described in CliVar as Likely_pathogenic. Clinvar id is 158990.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150592680-A-T is described in CliVar as Likely_pathogenic. Clinvar id is 158990.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150592680-A-T is described in CliVar as Likely_pathogenic. Clinvar id is 158990.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150592680-A-T is described in CliVar as Likely_pathogenic. Clinvar id is 158990.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150592680-A-T is described in CliVar as Likely_pathogenic. Clinvar id is 158990.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150592680-A-T is described in CliVar as Likely_pathogenic. Clinvar id is 158990.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150592680-A-T is described in CliVar as Likely_pathogenic. Clinvar id is 158990.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150592680-A-T is described in CliVar as Likely_pathogenic. Clinvar id is 158990.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150592680-A-T is described in CliVar as Likely_pathogenic. Clinvar id is 158990.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150592680-A-T is described in CliVar as Likely_pathogenic. Clinvar id is 158990.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150592680-A-T is described in CliVar as Likely_pathogenic. Clinvar id is 158990.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150592680-A-T is described in CliVar as Likely_pathogenic. Clinvar id is 158990.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150592680-A-T is described in CliVar as Likely_pathogenic. Clinvar id is 158990.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150592680-A-T is described in CliVar as Likely_pathogenic. Clinvar id is 158990.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150592680-A-T is described in CliVar as Likely_pathogenic. Clinvar id is 158990.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150592680-A-T is described in CliVar as Likely_pathogenic. Clinvar id is 158990.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150592680-A-T is described in CliVar as Likely_pathogenic. Clinvar id is 158990.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150592680-A-T is described in CliVar as Likely_pathogenic. Clinvar id is 158990.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150592680-A-T is described in CliVar as Likely_pathogenic. Clinvar id is 158990.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150592680-A-T is described in CliVar as Likely_pathogenic. Clinvar id is 158990.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150592680-A-T is described in CliVar as Likely_pathogenic. Clinvar id is 158990.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150592680-A-T is described in CliVar as Likely_pathogenic. Clinvar id is 158990.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150592680-A-T is described in CliVar as Likely_pathogenic. Clinvar id is 158990.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150592680-A-T is described in CliVar as Likely_pathogenic. Clinvar id is 158990.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150592680-A-T is described in CliVar as Likely_pathogenic. Clinvar id is 158990.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150592680-A-T is described in CliVar as Likely_pathogenic. Clinvar id is 158990.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150592680-A-T is described in CliVar as Likely_pathogenic. Clinvar id is 158990.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150592680-A-T is described in CliVar as Likely_pathogenic. Clinvar id is 158990.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150592680-A-T is described in CliVar as Likely_pathogenic. Clinvar id is 158990.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150592680-A-T is described in CliVar as Likely_pathogenic. Clinvar id is 158990.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150592680-A-T is described in CliVar as Likely_pathogenic. Clinvar id is 158990.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150592680-A-T is described in CliVar as Likely_pathogenic. Clinvar id is 158990.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150592680-A-T is described in CliVar as Likely_pathogenic. Clinvar id is 158990.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150592680-A-T is described in CliVar as Likely_pathogenic. Clinvar id is 158990.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150592680-A-T is described in CliVar as Likely_pathogenic. Clinvar id is 158990.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150592680-A-T is described in CliVar as Likely_pathogenic. Clinvar id is 158990.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150592680-A-T is described in CliVar as Likely_pathogenic. Clinvar id is 158990.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150592680-A-T is described in CliVar as Likely_pathogenic. Clinvar id is 158990.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150592680-A-T is described in CliVar as Likely_pathogenic. Clinvar id is 158990.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150592680-A-T is described in CliVar as Likely_pathogenic. Clinvar id is 158990.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.63+3A>T		splice_region_variant, intron_variant	Intron 2 of 14	ENST00000370396.7	NP_000243.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTM1	ENST00000370396.7	c.63+3A>T		splice_region_variant, intron_variant	Intron 2 of 14	1	NM_000252.3	ENSP00000359423.3

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 22

GnomAD4 genome Cov.: 23

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Severe X-linked myotubular myopathy Pathogenic:1

Feb 08, 2013

Genetic Services Laboratory, University of Chicago

Significance: Likely pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
CADD	Benign	13
DANN	Benign	0.93
PhyloP100		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Pathogenic	0.95
SpliceAI score (max)		0.77		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.77		Position offset: -3

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

Other links and lift over

dbSNP: rs587783844; hg19: chrX-149761142;