Variant X-150592646-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_000252.3(MTM1):c.32C>T(p.Ser11Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000102 in 1,081,141 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 6 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 0.000010 ( 0 hom. 6 hem. )

Consequence

MTM1
NM_000252.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.15

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High Hemizygotes in GnomAdExome4 at 6 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTM1	NM_000252.3 link	c.32C>T	p.Ser11Leu	missense_variant	2/15	ENST00000370396.7	NP_000243.1	Q13496-1A0A024RC06

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTM1	ENST00000370396.7 link	c.32C>T	p.Ser11Leu	missense_variant	2/15	1	NM_000252.3	ENSP00000359423.3		Q13496-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000109

AC:

AN:

182786

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

67358

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000245

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000102

AC:

AN:

1081141

Hom.:

Cov.:

AF XY:

0.0000172

AC XY:

AN XY:

348247

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000121

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Severe X-linked myotubular myopathy

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jun 20, 2022

This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 11 of the MTM1 protein (p.Ser11Leu). This variant is present in population databases (rs782293228, gnomAD 0.003%), including at least one homozygous and/or hemizygous individual. This variant has not been reported in the literature in individuals affected with MTM1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Pathogenic

0.35

BayesDel_noAF

Pathogenic

0.31

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.42

T;.

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.92

D;D

M_CAP

Pathogenic

0.90

MetaRNN

Uncertain

0.51

D;D

MetaSVM

Pathogenic

0.82

MutationAssessor

Uncertain

2.9

M;.

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-1.9

N;D

REVEL

Uncertain

0.58

Sift

Benign

0.038

D;D

Sift4G

Uncertain

0.038

D;D

Polyphen

0.45

B;.

Vest4

0.47

MutPred

0.30

Gain of relative solvent accessibility (P = 0.005);Gain of relative solvent accessibility (P = 0.005);

MVP

0.95

MPC

0.69

ClinPred

0.54

GERP RS

5.7

Varity_R

0.26

gMVP

0.80

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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