rs184956219

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_000252.3(MTM1):c.64-14T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00537 in 1,194,712 control chromosomes in the GnomAD database, including 18 homozygotes. There are 2,126 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0034 ( 0 hom., 103 hem., cov: 23)

Exomes 𝑓: 0.0056 ( 18 hom. 2023 hem. )

Consequence

MTM1
NM_000252.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.123

Publications

1 publications found

Variant links:

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

MTM1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant X-150596484-T-C is Benign according to our data. Variant chrX-150596484-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 158992.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00343 (384/112039) while in subpopulation NFE AF = 0.00539 (287/53241). AF 95% confidence interval is 0.00488. There are 0 homozygotes in GnomAd4. There are 103 alleles in the male GnomAd4 subpopulation. Median coverage is 23. This position passed quality control check.

BS2

High Hemizygotes in GnomAd4 at 103 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTM1	NM_000252.3 link	c.64-14T>C		intron_variant	Intron 2 of 14	ENST00000370396.7	NP_000243.1	Q13496-1A0A024RC06

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTM1	ENST00000370396.7 link	c.64-14T>C		intron_variant	Intron 2 of 14	1	NM_000252.3	ENSP00000359423.3		Q13496-1

Frequencies

GnomAD3 genomes

AF:

0.00344

AC:

385

AN:

111993

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000975

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00190

Gnomad ASJ

AF:

0.00565

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00518

Gnomad FIN

AF:

0.000657

Gnomad MID

AF:

0.0168

Gnomad NFE

AF:

0.00539

Gnomad OTH

AF:

0.00731

GnomAD2 exomes

AF:

0.00466

AC:

851

AN:

182505

AF XY:

0.00542

show subpopulations

Gnomad AFR exome

AF:

0.00107

Gnomad AMR exome

AF:

0.00183

Gnomad ASJ exome

AF:

0.00496

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00133

Gnomad NFE exome

AF:

0.00636

Gnomad OTH exome

AF:

0.00377

GnomAD4 exome

AF:

0.00557

AC:

6033

AN:

1082673

Hom.:

Cov.:

AF XY:

0.00577

AC XY:

2023

AN XY:

350577

show subpopulations

African (AFR)

AF:

0.000881

AC:

AN:

26103

American (AMR)

AF:

0.00159

AC:

AN:

35158

Ashkenazi Jewish (ASJ)

AF:

0.00638

AC:

123

AN:

19274

East Asian (EAS)

AF:

0.00

AC:

AN:

30107

South Asian (SAS)

AF:

0.0106

AC:

569

AN:

53712

European-Finnish (FIN)

AF:

0.00141

AC:

AN:

40396

Middle Eastern (MID)

AF:

0.00969

AC:

AN:

3096

European-Non Finnish (NFE)

AF:

0.00594

AC:

4923

AN:

829335

Other (OTH)

AF:

0.00554

AC:

252

AN:

45492

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

167

333

500

666

833

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

194

388

582

776

970

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00343

AC:

384

AN:

112039

Hom.:

Cov.:

AF XY:

0.00301

AC XY:

103

AN XY:

34195

show subpopulations

African (AFR)

AF:

0.000973

AC:

AN:

30844

American (AMR)

AF:

0.00190

AC:

AN:

10525

Ashkenazi Jewish (ASJ)

AF:

0.00565

AC:

AN:

2653

East Asian (EAS)

AF:

0.00

AC:

AN:

3572

South Asian (SAS)

AF:

0.00520

AC:

AN:

2691

European-Finnish (FIN)

AF:

0.000657

AC:

AN:

6089

Middle Eastern (MID)

AF:

0.0138

AC:

AN:

217

European-Non Finnish (NFE)

AF:

0.00539

AC:

287

AN:

53241

Other (OTH)

AF:

0.00722

AC:

AN:

1523

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00422

Hom.:

Bravo

AF:

0.00317

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Jul 10, 2015

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 08, 2013

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 29, 2016

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Severe X-linked myotubular myopathy

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

2.6

(source)

DANN

Benign

0.57

PhyloP100

0.12

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over