rs191553188

Variant names:

• chrX-150596579-C-T
• rs191553188
• NM_000252.3:c.136+9C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_000252.3(MTM1):​c.136+9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000597 in 1,193,665 control chromosomes in the GnomAD database, including 3 homozygotes. There are 189 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0031 (2 hom., 95 hem., cov: 23)
  • Exomes 𝑓: 0.00034 (1 hom. 94 hem.)
• Consequence: MTM1 NM_000252.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:3
• Conservation: PhyloP100: 0.464
• Publications: 0 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: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant X-150596579-C-T is Benign according to our data. Variant chrX-150596579-C-T is described in ClinVar as Benign. ClinVar VariationId is 461695.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00309 (346/111991) while in subpopulation AFR AF = 0.0104 (321/30797). AF 95% confidence interval is 0.00948. There are 2 homozygotes in GnomAd4. There are 95 alleles in the male GnomAd4 subpopulation. Median coverage is 23. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTM1	NM_000252.3	c.136+9C>T		intron_variant	Intron 3 of 14	ENST00000370396.7	NP_000243.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTM1	ENST00000370396.7	c.136+9C>T		intron_variant	Intron 3 of 14	1	NM_000252.3	ENSP00000359423.3

Frequencies

GnomAD3 genomes AF: 0.00307 AC: 344 AN: 111937 Hom.: 2 Cov.: 23

Gnomad AFR AF: 0.0104

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00199

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000376

Gnomad OTH AF: 0.00134

GnomAD2 exomes AF: 0.000827 AC: 151 AN: 182686 AF XY: 0.000475

Gnomad AFR exome AF: 0.00966

Gnomad AMR exome AF: 0.000731

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000246

Gnomad OTH exome AF: 0.000222

GnomAD4 exome AF: 0.000339 AC: 367 AN: 1081674 Hom.: 1 Cov.: 26 AF XY: 0.000270 AC XY: 94 AN XY: 348012

African (AFR) AF: 0.0106 AC: 276 AN: 26062

American (AMR) AF: 0.000882 AC: 31 AN: 35164

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19262

East Asian (EAS) AF: 0.00 AC: 0 AN: 30110

South Asian (SAS) AF: 0.0000745 AC: 4 AN: 53725

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40463

Middle Eastern (MID) AF: 0.000520 AC: 2 AN: 3847

European-Non Finnish (NFE) AF: 0.00000846 AC: 7 AN: 827499

Other (OTH) AF: 0.00103 AC: 47 AN: 45542

GnomAD4 genome AF: 0.00309 AC: 346 AN: 111991 Hom.: 2 Cov.: 23 AF XY: 0.00278 AC XY: 95 AN XY: 34167

African (AFR) AF: 0.0104 AC: 321 AN: 30797

American (AMR) AF: 0.00199 AC: 21 AN: 10555

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2650

East Asian (EAS) AF: 0.00 AC: 0 AN: 3576

South Asian (SAS) AF: 0.00 AC: 0 AN: 2699

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6061

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 216

European-Non Finnish (NFE) AF: 0.0000376 AC: 2 AN: 53241

Other (OTH) AF: 0.00132 AC: 2 AN: 1516

Alfa AF: 0.00126 Hom.: 6

Bravo AF: 0.00350

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

-

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Severe X-linked myotubular myopathy Benign:1

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

-

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	14
DANN	Benign	0.66
PhyloP100		0.46
Mutation Taster		=100/0	polymorphism (auto)

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: rs191553188; hg19: chrX-149765043;