Variant rs184956219 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_000252.3(MTM1):c.64-14T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00537 in 1,194,712 control chromosomes in the GnomAD database, including 18 homozygotes. There are 2,126 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0034 ( 0 hom., 103 hem., cov: 23)

Exomes 𝑓: 0.0056 ( 18 hom. 2023 hem. )

Consequence

MTM1
NM_000252.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.123

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:

MTM1 (HGNC:):

MTM1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant X-150596484-T-C is Benign according to our data. Variant chrX-150596484-T-C is described in ClinVar as [Benign]. Clinvar id is 158992.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-150596484-T-C is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00343 (384/112039) while in subpopulation NFE AF= 0.00539 (287/53241). AF 95% confidence interval is 0.00488. There are 0 homozygotes in gnomad4. There are 103 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.

BS2

High Hemizygotes in GnomAd4 at 103 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTM1	NM_000252.3 linkuse as main transcript	c.64-14T>C		intron_variant		ENST00000370396.7	NP_000243.1	Q13496-1A0A024RC06

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTM1	ENST00000370396.7 linkuse as main transcript	c.64-14T>C		intron_variant		1	NM_000252.3	ENSP00000359423.3		Q13496-1

Frequencies

GnomAD3 genomes

AF:

0.00344

AC:

385

AN:

111993

Hom.:

Cov.:

AF XY:

0.00302

AC XY:

103

AN XY:

34139

show subpopulations

Gnomad AFR

AF:

0.000975

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00190

Gnomad ASJ

AF:

0.00565

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00518

Gnomad FIN

AF:

0.000657

Gnomad MID

AF:

0.0168

Gnomad NFE

AF:

0.00539

Gnomad OTH

AF:

0.00731

GnomAD3 exomes

AF:

0.00466

AC:

851

AN:

182505

Hom.:

AF XY:

0.00542

AC XY:

364

AN XY:

67097

show subpopulations

Gnomad AFR exome

AF:

0.00107

Gnomad AMR exome

AF:

0.00183

Gnomad ASJ exome

AF:

0.00496

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0103

Gnomad FIN exome

AF:

0.00133

Gnomad NFE exome

AF:

0.00636

Gnomad OTH exome

AF:

0.00377

GnomAD4 exome

AF:

0.00557

AC:

6033

AN:

1082673

Hom.:

Cov.:

AF XY:

0.00577

AC XY:

2023

AN XY:

350577

show subpopulations

Gnomad4 AFR exome

AF:

0.000881

Gnomad4 AMR exome

AF:

0.00159

Gnomad4 ASJ exome

AF:

0.00638

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0106

Gnomad4 FIN exome

AF:

0.00141

Gnomad4 NFE exome

AF:

0.00594

Gnomad4 OTH exome

AF:

0.00554

GnomAD4 genome

AF:

0.00343

AC:

384

AN:

112039

Hom.:

Cov.:

AF XY:

0.00301

AC XY:

103

AN XY:

34195

show subpopulations

Gnomad4 AFR

AF:

0.000973

Gnomad4 AMR

AF:

0.00190

Gnomad4 ASJ

AF:

0.00565

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00520

Gnomad4 FIN

AF:

0.000657

Gnomad4 NFE

AF:

0.00539

Gnomad4 OTH

AF:

0.00722

Alfa

AF:

0.00422

Hom.:

Bravo

AF:

0.00317

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jul 10, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Feb 08, 2013	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 29, 2016	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

Jan 31, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

2.6

DANN

Benign

0.57

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