rs587783809

chrX-150598663-C-T

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.208C>T(p.Leu70Phe) variant causes a missense 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 (★).

• Frequency: Genomes: not found (cov: 24)
• Consequence: MTM1 NM_000252.3 missense
• Clinical Significance: Pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 2.86

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]

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, 0.965
• PP5: Variant X-150598663-C-T is Pathogenic according to our data. Variant chrX-150598663-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 158955.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150598663-C-T is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTM1	NM_000252.3	c.208C>T	p.Leu70Phe	missense_variant	4/15	ENST00000370396.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTM1	ENST00000370396.7	c.208C>T	p.Leu70Phe	missense_variant	4/15	1	NM_000252.3	P1

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Cov.: 25

GnomAD4 genome Cov.: 24

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Severe X-linked myotubular myopathy Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Feb 08, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.45
BayesDel_addAF	Pathogenic	0.53	D
BayesDel_noAF	Pathogenic	0.53
Cadd	Pathogenic	27
Dann	Pathogenic	1.0
DEOGEN2	Pathogenic	0.92	D;.
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Pathogenic	0.98	D;D
M_CAP	Pathogenic	0.86	D
MetaRNN	Pathogenic	0.96	D;D
MetaSVM	Pathogenic	0.89	D
MutationAssessor	Uncertain	2.8	M;.
MutationTaster	Benign	0.99	D;D;D;D
PrimateAI	Uncertain	0.76	T
PROVEAN	Uncertain	-3.6	D;D
REVEL	Pathogenic	0.85
Sift	Benign	0.055	T;D
Sift4G	Benign	0.12	T;D
Polyphen		1.0	D;.
Vest4		0.96
MutPred		0.86		Loss of catalytic residue at L70 (P = 0.0223);Loss of catalytic residue at L70 (P = 0.0223);
MVP		0.99
MPC		1.7
ClinPred		0.99	D
GERP RS		4.6
Varity_R		0.96
gMVP		0.97

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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: rs587783809; hg19: chrX-149767127;