NM_000252.3:c.420C>G

Variant names:

• chrX-150619115-C-G
• rs587783825
• NM_000252.3:c.420C>G

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.420C>G​(p.Tyr140*) 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 Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. Y140Y) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 22)
• Consequence: MTM1 NM_000252.3 stop_gained
• Clinical Significance: Pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 0.467
• Publications: 1 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-150619115-C-G is Pathogenic according to our data. Variant chrX-150619115-C-G is described in CliVar as Pathogenic. Clinvar id is 158971.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150619115-C-G is described in CliVar as Pathogenic. Clinvar id is 158971.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150619115-C-G is described in CliVar as Pathogenic. Clinvar id is 158971.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150619115-C-G is described in CliVar as Pathogenic. Clinvar id is 158971.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150619115-C-G is described in CliVar as Pathogenic. Clinvar id is 158971.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150619115-C-G is described in CliVar as Pathogenic. Clinvar id is 158971.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150619115-C-G is described in CliVar as Pathogenic. Clinvar id is 158971.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150619115-C-G is described in CliVar as Pathogenic. Clinvar id is 158971.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150619115-C-G is described in CliVar as Pathogenic. Clinvar id is 158971.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150619115-C-G is described in CliVar as Pathogenic. Clinvar id is 158971.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150619115-C-G is described in CliVar as Pathogenic. Clinvar id is 158971.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150619115-C-G is described in CliVar as Pathogenic. Clinvar id is 158971.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150619115-C-G is described in CliVar as Pathogenic. Clinvar id is 158971.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150619115-C-G is described in CliVar as Pathogenic. Clinvar id is 158971.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150619115-C-G is described in CliVar as Pathogenic. Clinvar id is 158971.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150619115-C-G is described in CliVar as Pathogenic. Clinvar id is 158971.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150619115-C-G is described in CliVar as Pathogenic. Clinvar id is 158971.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150619115-C-G is described in CliVar as Pathogenic. Clinvar id is 158971.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150619115-C-G is described in CliVar as Pathogenic. Clinvar id is 158971.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150619115-C-G is described in CliVar as Pathogenic. Clinvar id is 158971.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150619115-C-G is described in CliVar as Pathogenic. Clinvar id is 158971.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150619115-C-G is described in CliVar as Pathogenic. Clinvar id is 158971.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150619115-C-G is described in CliVar as Pathogenic. Clinvar id is 158971.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150619115-C-G is described in CliVar as Pathogenic. Clinvar id is 158971.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150619115-C-G is described in CliVar as Pathogenic. Clinvar id is 158971.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150619115-C-G is described in CliVar as Pathogenic. Clinvar id is 158971.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150619115-C-G is described in CliVar as Pathogenic. Clinvar id is 158971.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150619115-C-G is described in CliVar as Pathogenic. Clinvar id is 158971.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150619115-C-G is described in CliVar as Pathogenic. Clinvar id is 158971.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150619115-C-G is described in CliVar as Pathogenic. Clinvar id is 158971.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150619115-C-G is described in CliVar as Pathogenic. Clinvar id is 158971.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150619115-C-G is described in CliVar as Pathogenic. Clinvar id is 158971.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150619115-C-G is described in CliVar as Pathogenic. Clinvar id is 158971.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150619115-C-G is described in CliVar as Pathogenic. Clinvar id is 158971.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150619115-C-G is described in CliVar as Pathogenic. Clinvar id is 158971.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150619115-C-G is described in CliVar as Pathogenic. Clinvar id is 158971.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150619115-C-G is described in CliVar as Pathogenic. Clinvar id is 158971.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150619115-C-G is described in CliVar as Pathogenic. Clinvar id is 158971.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150619115-C-G is described in CliVar as Pathogenic. Clinvar id is 158971.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150619115-C-G is described in CliVar as Pathogenic. Clinvar id is 158971.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150619115-C-G is described in CliVar as Pathogenic. Clinvar id is 158971.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150619115-C-G is described in CliVar as Pathogenic. Clinvar id is 158971.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150619115-C-G is described in CliVar as Pathogenic. Clinvar id is 158971.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150619115-C-G is described in CliVar as Pathogenic. Clinvar id is 158971.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150619115-C-G is described in CliVar as Pathogenic. Clinvar id is 158971.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150619115-C-G is described in CliVar as Pathogenic. Clinvar id is 158971.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150619115-C-G is described in CliVar as Pathogenic. Clinvar id is 158971.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150619115-C-G is described in CliVar as Pathogenic. Clinvar id is 158971.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.420C>G	p.Tyr140*	stop_gained	Exon 6 of 15	ENST00000370396.7	NP_000243.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTM1	ENST00000370396.7	c.420C>G	p.Tyr140*	stop_gained	Exon 6 of 15	1	NM_000252.3	ENSP00000359423.3

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 22

ClinVar

Significance: 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: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.74	D
BayesDel_noAF	Pathogenic	0.54
CADD	Pathogenic	32
DANN	Uncertain	0.99
FATHMM_MKL	Uncertain	0.89	D
PhyloP100		0.47
Vest4		0.94
GERP RS		-4.1
Mutation Taster		=1/199	disease causing (ClinVar)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.29		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.29		Position offset: 24

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

Other links and lift over

dbSNP: rs587783825; hg19: chrX-149787588;