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 (★). The gene MTM1 is included in the ClinGen Criteria Specification Registry.

• 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: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Orphanet, ClinGen, G2P, Myriad Women’s Health, Ambry Genetics

ACMG classification

Specifications for MTM1 are available in the ClinGen Criteria Specification Registry and recommended for reference when assigning criteria.

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

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.136+9C>T		intron	N/A	NP_000243.1	Q13496-1
	MTM1	NM_001376908.1		c.136+9C>T		intron	N/A	NP_001363837.1	Q13496-1
	MTM1	NM_001376906.1		c.136+9C>T		intron	N/A	NP_001363835.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTM1	ENST00000370396.7	TSL:1 MANE Select	c.136+9C>T		intron	N/A	ENSP00000359423.3	Q13496-1
	MTM1	ENST00000689314.1		c.136+9C>T		intron	N/A	ENSP00000510607.1	A0A8I5KZ76
	MTM1	ENST00000866458.1		c.136+9C>T		intron	N/A	ENSP00000536517.1

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)
-	-	1	Severe X-linked myotubular myopathy (1)

Computational scores

Source: dbNSFP v4.9

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;