rs587783862

Variant names:

• chrX-150649766-TTTC-T
• rs587783862
• NM_000252.3:c.924_926delCTT

Variant summary

Our verdict is Uncertain significance. The variant received 5 ACMG points: 5P and 0B. PM2 PM4_Supporting PP5_Moderate

The NM_000252.3(MTM1):​c.924_926delCTT​(p.Phe308del) variant causes a disruptive inframe deletion change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: MTM1 NM_000252.3 disruptive_inframe_deletion
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 4.19
• 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: Uncertain_significance. The variant received 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_000252.3. Strenght limited to Supporting due to length of the change: 1aa.
• PP5: Variant X-150649766-TTTC-T is Pathogenic according to our data. Variant chrX-150649766-TTTC-T is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 159009.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000252.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTM1	NM_000252.3	MANE Select	c.924_926delCTT	p.Phe308del	disruptive_inframe_deletion	Exon 10 of 15	NP_000243.1
	MTM1	NM_001376908.1		c.924_926delCTT	p.Phe308del	disruptive_inframe_deletion	Exon 10 of 15	NP_001363837.1
	MTM1	NM_001376906.1		c.924_926delCTT	p.Phe308del	disruptive_inframe_deletion	Exon 10 of 15	NP_001363835.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTM1	ENST00000370396.7	TSL:1 MANE Select	c.924_926delCTT	p.Phe308del	disruptive_inframe_deletion	Exon 10 of 15	ENSP00000359423.3
	MTM1	ENST00000689314.1		c.969_971delCTT	p.Phe323del	disruptive_inframe_deletion	Exon 11 of 16	ENSP00000510607.1
	MTM1	ENST00000685944.1		c.924_926delCTT	p.Phe308del	disruptive_inframe_deletion	Exon 10 of 15	ENSP00000509266.1

Frequencies

GnomAD3 genomes Cov.: 23

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 23

ClinVar

ClinVar submissions as Germline

Significance: Likely pathogenic

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
1	-	-	Severe X-linked myotubular myopathy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.2
Mutation Taster		=71/29	disease causing (ClinVar)

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

Other links and lift over

dbSNP: rs587783862; hg19: chrX-149818239;