Genetic Variant MTM1:c.1260+17A>G (chrX-150658044-A-G) – ACMG Classification: Benign (-20 pts)

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.1260+17A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00896 in 1,115,153 control chromosomes in the GnomAD database, including 44 homozygotes. There are 3,073 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0066 ( 5 hom., 237 hem., cov: 23)

Exomes 𝑓: 0.0092 ( 39 hom. 2836 hem. )

Consequence

MTM1
NM_000252.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.607

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant X-150658044-A-G is Benign according to our data. Variant chrX-150658044-A-G is described in ClinVar as Benign. ClinVar VariationId is 255621.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 = 0.00661 (744/112605) while in subpopulation NFE AF = 0.00885 (472/53326). AF 95% confidence interval is 0.00819. There are 5 homozygotes in GnomAd4. There are 237 alleles in the male GnomAd4 subpopulation. Median coverage is 23. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 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.1260+17A>G	intron	N/A	NP_000243.1
MTM1	NM_001376908.1		c.1260+17A>G	intron	N/A	NP_001363837.1
MTM1	NM_001376906.1		c.1260+17A>G	intron	N/A	NP_001363835.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
MTM1	ENST00000370396.7	TSL:1 MANE Select	c.1260+17A>G	intron	N/A	ENSP00000359423.3
MTM1	ENST00000689314.1		c.1305+17A>G	intron	N/A	ENSP00000510607.1
MTM1	ENST00000685944.1		c.1260+17A>G	intron	N/A	ENSP00000509266.1

Frequencies

GnomAD3 genomes

AF:

0.00661

AC:

744

AN:

112551

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00145

Gnomad AMI

AF:

0.0701

Gnomad AMR

AF:

0.00198

Gnomad ASJ

AF:

0.00188

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0232

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00885

Gnomad OTH

AF:

0.00725

GnomAD2 exomes

AF:

0.00670

AC:

1169

AN:

174442

AF XY:

0.00651

show subpopulations

Gnomad AFR exome

AF:

0.00127

Gnomad AMR exome

AF:

0.00337

Gnomad ASJ exome

AF:

0.00273

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0190

Gnomad NFE exome

AF:

0.00925

Gnomad OTH exome

AF:

0.00368

GnomAD4 exome

AF:

0.00922

AC:

9246

AN:

1002548

Hom.:

Cov.:

AF XY:

0.00996

AC XY:

2836

AN XY:

284744

show subpopulations

African (AFR)

AF:

0.000741

AC:

AN:

24305

American (AMR)

AF:

0.00289

AC:

101

AN:

34915

Ashkenazi Jewish (ASJ)

AF:

0.00197

AC:

AN:

18750

East Asian (EAS)

AF:

0.00

AC:

AN:

29744

South Asian (SAS)

AF:

0.00175

AC:

AN:

51385

European-Finnish (FIN)

AF:

0.0175

AC:

706

AN:

40240

Middle Eastern (MID)

AF:

0.000770

AC:

AN:

3896

European-Non Finnish (NFE)

AF:

0.0106

AC:

7991

AN:

756348

Other (OTH)

AF:

0.00698

AC:

300

AN:

42965

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

312

624

937

1249

1561

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

314

628

942

1256

1570

<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:

0.00661

AC:

744

AN:

112605

Hom.:

Cov.:

AF XY:

0.00682

AC XY:

237

AN XY:

34747

show subpopulations

African (AFR)

AF:

0.00145

AC:

AN:

31035

American (AMR)

AF:

0.00197

AC:

AN:

10636

Ashkenazi Jewish (ASJ)

AF:

0.00188

AC:

AN:

2659

East Asian (EAS)

AF:

0.00

AC:

AN:

3613

South Asian (SAS)

AF:

0.00

AC:

AN:

2767

European-Finnish (FIN)

AF:

0.0232

AC:

142

AN:

6130

Middle Eastern (MID)

AF:

0.00

AC:

AN:

218

European-Non Finnish (NFE)

AF:

0.00885

AC:

472

AN:

53326

Other (OTH)

AF:

0.00716

AC:

AN:

1536

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

103

129

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:

0.00689

Hom.:

Bravo

AF:

0.00544

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

May 12, 2016

Eurofins Ntd Llc (ga)

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

Mar 07, 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

Jan 27, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.022

(source)

DANN

Benign

0.70

PhyloP100

-0.61

Mutation Taster

=100/0

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over