rs878853108

Variant names:

• chrX-150641303-TTAA-T
• rs878853108
• NM_000252.3:c.567_569delTAA

Variant summary

Our verdict is Likely pathogenic. The variant received 7 ACMG points: 7P and 0B. PM1 PM2 PM4_Supporting PP5_Moderate

The NM_000252.3(MTM1):​c.567_569delTAA​(p.Asn189del) variant causes a disruptive inframe deletion change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★).

• Frequency: Genomes: not found (cov: 22)
• Consequence: MTM1 NM_000252.3 disruptive_inframe_deletion
• Clinical Significance: Pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 8.82
• Publications: 2 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: Genomics England PanelApp, ClinGen, Labcorp Genetics (formerly Invitae), Myriad Women’s Health, Ambry Genetics, G2P, Orphanet

ACMG classification

Our verdict: Likely_pathogenic. The variant received 7 ACMG points.

• PM1: In a hotspot region, there are 5 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 7 uncertain in NM_000252.3
• 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-150641303-TTAA-T is Pathogenic according to our data. Variant chrX-150641303-TTAA-T is described in ClinVar as Pathogenic. ClinVar VariationId is 235767.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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTM1	NM_000252.3	MANE Select	c.567_569delTAA	p.Asn189del	disruptive_inframe_deletion	Exon 8 of 15	NP_000243.1	Q13496-1
	MTM1	NM_001376908.1		c.567_569delTAA	p.Asn189del	disruptive_inframe_deletion	Exon 8 of 15	NP_001363837.1	Q13496-1
	MTM1	NM_001376906.1		c.567_569delTAA	p.Asn189del	disruptive_inframe_deletion	Exon 8 of 15	NP_001363835.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTM1	ENST00000370396.7	TSL:1 MANE Select	c.567_569delTAA	p.Asn189del	disruptive_inframe_deletion	Exon 8 of 15	ENSP00000359423.3	Q13496-1
	MTM1	ENST00000689314.1		c.612_614delTAA	p.Asn204del	disruptive_inframe_deletion	Exon 9 of 16	ENSP00000510607.1	A0A8I5KZ76
	MTM1	ENST00000866458.1		c.612_614delTAA	p.Asn204del	disruptive_inframe_deletion	Exon 9 of 16	ENSP00000536517.1

Frequencies

GnomAD3 genomes Cov.: 22

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

GnomAD4 genome Cov.: 22

ClinVar

ClinVar submissions as Germline

Significance: Pathogenic

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
1	-	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		8.8
Mutation Taster		=5/95	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: rs878853108; hg19: chrX-149809776;