rs587783776

Positions:

• chrX-150659728-T-A

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM2 PP3_Strong PP5_Moderate

The NM_000252.3(MTM1):​c.1325T>A​(p.Ile442Asn) variant causes a missense 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. Variant has been reported in ClinVar as Likely pathogenic (★).

• Frequency: Genomes: not found (cov: 22)
• Consequence: MTM1 NM_000252.3 missense
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 7.97

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 (HGNC:):

ACMG classification

Verdict is Likely_pathogenic. Variant got 8 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.966
• PP5: Variant X-150659728-T-A is Pathogenic according to our data. Variant chrX-150659728-T-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 158918.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTM1	NM_000252.3	c.1325T>A	p.Ile442Asn	missense_variant	12/15	ENST00000370396.7	NP_000243.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTM1	ENST00000370396.7	c.1325T>A	p.Ile442Asn	missense_variant	12/15	1	NM_000252.3	ENSP00000359423.3

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 29

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

Likely pathogenic, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

May 29, 2014

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Pathogenic	0.37	D
BayesDel_noAF	Pathogenic	0.29
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Pathogenic	0.99	D
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Pathogenic	0.57	D
MetaRNN	Pathogenic	0.97	D
MetaSVM	Pathogenic	0.86	D
MutationAssessor	Pathogenic	3.5	H
PrimateAI	Uncertain	0.53	T
PROVEAN	Pathogenic	-6.1	D
REVEL	Pathogenic	0.84
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		0.97	D
Vest4		0.94
MutPred		0.75		Loss of stability (P = 0.0105);
MVP		0.97
MPC		1.8
ClinPred		1.0	D
GERP RS		4.1
Varity_R		0.96
gMVP		0.99

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs587783776; hg19: chrX-149828201;