Variant rs367912069 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4BA1BP7

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
ENST00000370396.7 synonymous

Scores

Clinical Significance

Benign reviewed by expert panel B:4

Conservation

PhyloP100: -0.303

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 -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/exons	MANE	Protein	UniProt
MTM1	NM_000252.3 linkuse as main transcript	c.582C>T	p.Leu194=	synonymous_variant	8/15	ENST00000370396.7	NP_000243.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTM1	ENST00000370396.7 linkuse as main transcript	c.582C>T	p.Leu194=	synonymous_variant	8/15	1	NM_000252.3	ENSP00000359423	P1	Q13496-1

Frequencies

GnomAD3 genomes

AF:

0.000314

AC:

AN:

111621

Hom.:

Cov.:

AF XY:

0.000207

AC XY:

AN XY:

33795

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

GnomAD3 exomes

AF:

0.000323

AC:

AN:

182841

Hom.:

AF XY:

0.000341

AC XY:

AN XY:

67525

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 SAS exome

AF:

0.00

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

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00278

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000238

Gnomad4 OTH exome

AF:

0.00128

GnomAD4 genome

AF:

0.000313

AC:

AN:

111674

Hom.:

Cov.:

AF XY:

0.000207

AC XY:

AN XY:

33858

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000569

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00791

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000655

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.000280

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: reviewed by expert panel

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

May 26, 2017

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

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Centronuclear myopathy

Benign:1

Benign, reviewed by expert panel

curation

ClinGen Congenital Myopathies Variant Curation Expert Panel, ClinGen

Aug 07, 2024

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

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 19, 2024

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

DANN

Benign

0.74

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

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