Genetic Variant MTM1:c.137-11dupT (chrX-150598574-C-CT) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP6_Very_StrongBS2

The NM_000252.3(MTM1):c.137-11dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000017 in 1,060,545 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 6 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., 1 hem., cov: 23)

Exomes 𝑓: 0.000016 ( 0 hom. 5 hem. )

Consequence

MTM1
NM_000252.3 intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.71

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP6

Variant X-150598574-C-CT is Benign according to our data. Variant chrX-150598574-C-CT is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 211531.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Hemizygotes in GnomAdExome4 at 5 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
MTM1	NM_000252.3	MANE Select	c.137-11dupT	intron	N/A	NP_000243.1
MTM1	NM_001376908.1		c.137-11dupT	intron	N/A	NP_001363837.1
MTM1	NM_001376906.1		c.137-11dupT	intron	N/A	NP_001363835.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
MTM1	ENST00000370396.7	TSL:1 MANE Select	c.137-18_137-17insT	intron	N/A	ENSP00000359423.3
MTM1	ENST00000689314.1		c.137-18_137-17insT	intron	N/A	ENSP00000510607.1
MTM1	ENST00000866458.1		c.137-18_137-17insT	intron	N/A	ENSP00000536517.1

Frequencies

GnomAD3 genomes

AF:

0.0000267

AC:

AN:

112176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000756

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000229

AC:

AN:

174696

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000279

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000257

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000158

AC:

AN:

948369

Hom.:

Cov.:

AF XY:

0.0000182

AC XY:

AN XY:

274611

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

23566

American (AMR)

AF:

0.00

AC:

AN:

34447

Ashkenazi Jewish (ASJ)

AF:

0.000327

AC:

AN:

18334

East Asian (EAS)

AF:

0.00

AC:

AN:

29356

South Asian (SAS)

AF:

0.00

AC:

AN:

50163

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40213

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3374

European-Non Finnish (NFE)

AF:

0.0000113

AC:

AN:

707951

Other (OTH)

AF:

0.0000244

AC:

AN:

40965

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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:

0.0000267

AC:

AN:

112176

Hom.:

Cov.:

AF XY:

0.0000291

AC XY:

AN XY:

34388

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30873

American (AMR)

AF:

0.00

AC:

AN:

10573

Ashkenazi Jewish (ASJ)

AF:

0.000756

AC:

AN:

2644

East Asian (EAS)

AF:

0.00

AC:

AN:

3622

South Asian (SAS)

AF:

0.00

AC:

AN:

2756

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6073

Middle Eastern (MID)

AF:

0.00

AC:

AN:

239

European-Non Finnish (NFE)

AF:

0.0000188

AC:

AN:

53199

Other (OTH)

AF:

0.00

AC:

AN:

1512

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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000151

ClinVar

ClinVar submissions as Germline

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Severe X-linked myotubular myopathy (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.7

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

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X-150598574-CT-CTT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over