Variant rs587783807 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

This summary comes from the ClinGen Evidence Repository: The c.1702A>G variant in MTM1 is a missense variant predicted to cause substitution of isoleucine by valine at amino acid 568. The highest population filtering allele frequency in gnomAD v4.1.0 is 0.00002629 (33/895101 alleles, 9 hemizygotes) in European (non-Finnish) population, which is higher than the ClinGen Congenital Myopathies VCEP threshold (≥0.000016) for BA1, and therefore meets this criterion (BA1). The computational predictor REVEL gives a score of 0.212, which is neither above nor below the thresholds predicting a damaging or benign impact on MTM1 function. In summary, this variant meets the criteria to be classified as benign for X-linked centronuclear myopathy based on the ACMG/AMP criteria applied, as specified by the ClinGen Congenital Myopathies VCEP: BA1. (Congenital Myopathies VCEP specifications version 1; 8/7/2024) LINK:https://erepo.genome.network/evrepo/ui/classification/CA172597/MONDO:0018947/149

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.000030 ( 0 hom. 9 hem. )

Consequence

MTM1
NM_000252.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.60

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BA1

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTM1	NM_000252.3 linkuse as main transcript	c.1702A>G	p.Ile568Val	missense_variant	15/15	ENST00000370396.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTM1	ENST00000370396.7 linkuse as main transcript	c.1702A>G	p.Ile568Val	missense_variant	15/15	1	NM_000252.3	P1	Q13496-1

Frequencies

GnomAD3 genomes

AF:

0.0000180

AC:

AN:

110829

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

32995

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000377

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000491

AC:

AN:

183296

Hom.:

AF XY:

0.0000295

AC XY:

AN XY:

67760

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000365

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000978

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000301

AC:

AN:

1098164

Hom.:

Cov.:

AF XY:

0.0000248

AC XY:

AN XY:

363526

show subpopulations

Gnomad4 AFR exome

AF:

0.0000379

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000368

Gnomad4 OTH exome

AF:

0.0000217

GnomAD4 genome

AF:

0.0000180

AC:

AN:

110829

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

32995

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000377

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000189

ExAC

AF:

0.0000330

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Feb 08, 2013

- -

Severe X-linked myotubular myopathy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 17, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Benign

0.38

DEOGEN2

Benign

0.29

FATHMM_MKL

Benign

0.70

LIST_S2

Benign

0.81

M_CAP

Uncertain

0.23

MetaRNN

Benign

0.14

MetaSVM

Benign

-0.45

MutationAssessor

Benign

0.40

MutationTaster

Benign

1.0

D;N;N;N

PrimateAI

Benign

0.41

PROVEAN

Benign

0.36

REVEL

Benign

0.21

Sift

Benign

0.56

Sift4G

Benign

0.38

Polyphen

0.0

Vest4

0.040

MutPred

0.23

Gain of methylation at K569 (P = 0.1314);

MVP

0.73

MPC

0.52

ClinPred

0.035

GERP RS

3.7

Varity_R

0.066

gMVP

0.33

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over