rs587783806

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2

The NM_000252.3(MTM1):c.1701C>T(p.Tyr567Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000437 in 1,208,934 control chromosomes in the GnomAD database, including 1 homozygotes. There are 276 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00019 ( 0 hom., 5 hem., cov: 22)

Exomes 𝑓: 0.00046 ( 1 hom. 271 hem. )

Consequence

MTM1
NM_000252.3 synonymous

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:2

Conservation

PhyloP100: 0.0740

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant X-150671484-C-T is Benign according to our data. Variant chrX-150671484-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 158951.We mark this variant Likely_benign, oryginal submission is: [Conflicting_classifications_of_pathogenicity].

BP7

Synonymous conserved (PhyloP=0.074 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.000189 (21/110831) while in subpopulation SAS AF = 0.00424 (11/2592). AF 95% confidence interval is 0.00238. There are 0 homozygotes in GnomAd4. There are 5 alleles in the male GnomAd4 subpopulation. Median coverage is 22. This position passed quality control check.

BS2

High Hemizygotes in GnomAd4 at 5 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTM1	NM_000252.3 link	c.1701C>T	p.Tyr567Tyr	synonymous_variant	Exon 15 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.1701C>T	p.Tyr567Tyr	synonymous_variant	Exon 15 of 15	1	NM_000252.3	ENSP00000359423.3		Q13496-1

Frequencies

GnomAD3 genomes

AF:

0.000190

AC:

AN:

110774

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000329

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000966

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000282

Gnomad SAS

AF:

0.00424

Gnomad FIN

AF:

0.000514

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000755

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000873

AC:

160

AN:

183272

AF XY:

0.00133

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000365

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000722

Gnomad FIN exome

AF:

0.000376

Gnomad NFE exome

AF:

0.000416

Gnomad OTH exome

AF:

0.00132

GnomAD4 exome

AF:

0.000462

AC:

507

AN:

1098103

Hom.:

Cov.:

AF XY:

0.000746

AC XY:

271

AN XY:

363465

show subpopulations

African (AFR)

AF:

0.0000379

AC:

AN:

26395

American (AMR)

AF:

0.0000284

AC:

AN:

35204

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19385

East Asian (EAS)

AF:

0.0000662

AC:

AN:

30206

South Asian (SAS)

AF:

0.00624

AC:

338

AN:

54147

European-Finnish (FIN)

AF:

0.000321

AC:

AN:

40502

Middle Eastern (MID)

AF:

0.00145

AC:

AN:

4137

European-Non Finnish (NFE)

AF:

0.000139

AC:

117

AN:

842033

Other (OTH)

AF:

0.000629

AC:

AN:

46094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

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:

0.000189

AC:

AN:

110831

Hom.:

Cov.:

AF XY:

0.000151

AC XY:

AN XY:

33015

show subpopulations

African (AFR)

AF:

0.0000328

AC:

AN:

30468

American (AMR)

AF:

0.0000964

AC:

AN:

10370

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2633

East Asian (EAS)

AF:

0.000283

AC:

AN:

3535

South Asian (SAS)

AF:

0.00424

AC:

AN:

2592

European-Finnish (FIN)

AF:

0.000514

AC:

AN:

5839

Middle Eastern (MID)

AF:

0.00

AC:

AN:

217

European-Non Finnish (NFE)

AF:

0.0000755

AC:

AN:

52997

Other (OTH)

AF:

0.00

AC:

AN:

1498

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.528

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:

0.000521

Hom.:

Bravo

AF:

0.0000982

EpiCase

AF:

0.000491

EpiControl

AF:

0.000415

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Severe X-linked myotubular myopathy

Uncertain:1Benign:2

Sep 16, 2020

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Feb 08, 2013

Genetic Services Laboratory, University of Chicago

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Dec 10, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

2.5

(source)

DANN

Benign

0.45

PhyloP100

0.074

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

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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