rs367912069

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP7BP4BA1

This summary comes from the ClinGen Evidence Repository: The variant NM_000252.3(MTM1):c.582C>T is a synonymous (silent) variant (p.Leu194=). The filtering allele frequency in gnomAD v4.1.0 is 0.002821 (112/33731 alleles, 2 homozygote, 36 hemizygotes) for the East Asian population, which is higher than the ClinGen congenital myopathy MTM1 threshold (≥0.000016) for BA1, and therefore meets this criterion (BA1). In addition, SpliceAI predicted no impact on splicing, meeting BP4/BP7 criteria. In summary, the variant meets criteria to be classified as benign. ACMG/AMP criteria met, as specified by the congenital myopathies VCEP: BA1, BP4, BP7 (ClinGen Congenital Myopathies VCEP specifications version 1; 8/7/2024). LINK:https://erepo.genome.network/evrepo/ui/classification/CA10539132/MONDO:0018947/149

Frequency

Genomes: 𝑓 0.00031 ( 2 hom., 7 hem., cov: 22)

Exomes 𝑓: 0.00013 ( 2 hom. 36 hem. )

Consequence

MTM1
NM_000252.3 synonymous

Scores

Clinical Significance

Benign reviewed by expert panel B:5

Conservation

PhyloP100: -0.303

Publications

0 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 -10 ACMG points.

BP4

For more information check the summary or visit ClinGen Evidence Repository.

BP7

For more information check the summary or visit ClinGen Evidence Repository.

BA1

For more information check the summary or visit ClinGen Evidence Repository.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTM1	NM_000252.3 link	c.582C>T	p.Leu194Leu	synonymous_variant	Exon 8 of 15	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.582C>T	p.Leu194Leu	synonymous_variant	Exon 8 of 15	1	NM_000252.3	ENSP00000359423.3		Q13496-1

Frequencies

GnomAD3 genomes

AF:

0.000314

AC:

AN:

111621

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000569

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00788

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000663

GnomAD2 exomes

AF:

0.000323

AC:

AN:

182841

AF XY:

0.000341

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00426

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000132

AC:

145

AN:

1097561

Hom.:

Cov.:

AF XY:

0.0000992

AC XY:

AN XY:

362971

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26380

American (AMR)

AF:

0.00

AC:

AN:

35199

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19383

East Asian (EAS)

AF:

0.00278

AC:

AN:

30190

South Asian (SAS)

AF:

0.00

AC:

AN:

54131

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40516

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4132

European-Non Finnish (NFE)

AF:

0.00000238

AC:

AN:

841563

Other (OTH)

AF:

0.00128

AC:

AN:

46067

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome 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

GnomAD4 genome

AF:

0.000313

AC:

AN:

111674

Hom.:

Cov.:

AF XY:

0.000207

AC XY:

AN XY:

33858

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30729

American (AMR)

AF:

0.000569

AC:

AN:

10553

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2647

East Asian (EAS)

AF:

0.00791

AC:

AN:

3541

South Asian (SAS)

AF:

0.00

AC:

AN:

2597

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6075

Middle Eastern (MID)

AF:

0.00

AC:

AN:

216

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53111

Other (OTH)

AF:

0.000655

AC:

AN:

1527

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

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:

0.000142

Hom.:

Bravo

AF:

0.000280

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: reviewed by expert panel

LINK: link

Submissions by phenotype

not specified

Benign:2

Jan 11, 2024

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 26, 2017

GeneDx

Significance:Likely 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

Jan 23, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Centronuclear myopathy

Benign:1

Aug 07, 2024

ClinGen Congenital Myopathies Variant Curation Expert Panel, ClinGen

Significance:Benign

Review Status:reviewed by expert panel

Collection Method:curation

The variant NM_000252.3(MTM1):c.582C>T is a synonymous (silent) variant (p.Leu194=). The filtering allele frequency in gnomAD v4.1.0 is 0.002821 (112/33731 alleles, 2 homozygote, 36 hemizygotes) for the East Asian population, which is higher than the ClinGen congenital myopathy MTM1 threshold (≥0.000016) for BA1, and therefore meets this criterion (BA1). In addition, SpliceAI predicted no impact on splicing, meeting BP4/BP7 criteria. In summary, the variant meets criteria to be classified as benign. ACMG/AMP criteria met, as specified by the congenital myopathies VCEP: BA1, BP4, BP7 (ClinGen Congenital Myopathies VCEP specifications version 1; 8/7/2024). -

MTM1-related disorder

Benign:1

Feb 19, 2024

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.35

CADD

Benign

5.9

(source)

DANN

Benign

0.74

PhyloP100

-0.30

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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