Variant X-150592630-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_000252.3(MTM1):c.16A>G(p.Thr6Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000276 in 1,086,099 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. T6T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., 0 hem., cov: 22)

Exomes 𝑓: 0.0000028 ( 0 hom. 1 hem. )

Failed GnomAD Quality Control

Consequence

MTM1
NM_000252.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0980

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 -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08551869).

BP6

Variant X-150592630-A-G is Benign according to our data. Variant chrX-150592630-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2992698.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTM1	NM_000252.3 linkuse as main transcript	c.16A>G	p.Thr6Ala	missense_variant	2/15	ENST00000370396.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTM1	ENST00000370396.7 linkuse as main transcript	c.16A>G	p.Thr6Ala	missense_variant	2/15	1	NM_000252.3	P1	Q13496-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

111799

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33975

FAILED QC

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000547

AC:

AN:

182770

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

67344

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:

0.0000525

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000276

AC:

AN:

1086099

Hom.:

Cov.:

AF XY:

0.00000284

AC XY:

AN XY:

352589

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:

0.0000186

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000241

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

111799

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33975

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:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Severe X-linked myotubular myopathy

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jan 30, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.059

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.34

Cadd

Benign

1.9

Dann

Benign

0.40

DEOGEN2

Benign

0.34

T;.

FATHMM_MKL

Benign

0.080

LIST_S2

Benign

0.57

T;T

M_CAP

Benign

0.057

MetaRNN

Benign

0.086

T;T

MetaSVM

Benign

-0.44

MutationAssessor

Benign

1.0

L;.

MutationTaster

Benign

1.0

D;D;N;N

PrimateAI

Benign

0.30

PROVEAN

Benign

-1.2

N;N

REVEL

Uncertain

0.30

Sift

Benign

0.66

T;T

Sift4G

Benign

0.70

T;T

Polyphen

0.0

B;.

Vest4

0.074

MutPred

0.11

Loss of phosphorylation at T6 (P = 0.0308);Loss of phosphorylation at T6 (P = 0.0308);

MVP

0.83

MPC

0.61

ClinPred

0.0091

GERP RS

-1.0

Varity_R

0.047

gMVP

0.64

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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