Variant rs185258809 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.1260+17A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00896 in 1,115,153 control chromosomes in the GnomAD database, including 44 homozygotes. There are 3,073 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0066 ( 5 hom., 237 hem., cov: 23)

Exomes 𝑓: 0.0092 ( 39 hom. 2836 hem. )

Consequence

MTM1
NM_000252.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.607

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 Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant X-150658044-A-G is Benign according to our data. Variant chrX-150658044-A-G is described in ClinVar as [Benign]. Clinvar id is 255621.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-150658044-A-G is described in Lovd as [Likely_benign]. Variant chrX-150658044-A-G is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00661 (744/112605) while in subpopulation NFE AF= 0.00885 (472/53326). AF 95% confidence interval is 0.00819. There are 5 homozygotes in gnomad4. There are 237 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 5 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTM1	NM_000252.3 linkuse as main transcript	c.1260+17A>G		intron_variant		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.1260+17A>G		intron_variant		1	NM_000252.3	ENSP00000359423	P1	Q13496-1

Frequencies

GnomAD3 genomes

AF:

0.00661

AC:

744

AN:

112551

Hom.:

Cov.:

AF XY:

0.00683

AC XY:

237

AN XY:

34683

show subpopulations

Gnomad AFR

AF:

0.00145

Gnomad AMI

AF:

0.0701

Gnomad AMR

AF:

0.00198

Gnomad ASJ

AF:

0.00188

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0232

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00885

Gnomad OTH

AF:

0.00725

GnomAD3 exomes

AF:

0.00670

AC:

1169

AN:

174442

Hom.:

AF XY:

0.00651

AC XY:

399

AN XY:

61330

show subpopulations

Gnomad AFR exome

AF:

0.00127

Gnomad AMR exome

AF:

0.00337

Gnomad ASJ exome

AF:

0.00273

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00138

Gnomad FIN exome

AF:

0.0190

Gnomad NFE exome

AF:

0.00925

Gnomad OTH exome

AF:

0.00368

GnomAD4 exome

AF:

0.00922

AC:

9246

AN:

1002548

Hom.:

Cov.:

AF XY:

0.00996

AC XY:

2836

AN XY:

284744

show subpopulations

Gnomad4 AFR exome

AF:

0.000741

Gnomad4 AMR exome

AF:

0.00289

Gnomad4 ASJ exome

AF:

0.00197

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00175

Gnomad4 FIN exome

AF:

0.0175

Gnomad4 NFE exome

AF:

0.0106

Gnomad4 OTH exome

AF:

0.00698

GnomAD4 genome

AF:

0.00661

AC:

744

AN:

112605

Hom.:

Cov.:

AF XY:

0.00682

AC XY:

237

AN XY:

34747

show subpopulations

Gnomad4 AFR

AF:

0.00145

Gnomad4 AMR

AF:

0.00197

Gnomad4 ASJ

AF:

0.00188

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0232

Gnomad4 NFE

AF:

0.00885

Gnomad4 OTH

AF:

0.00716

Alfa

AF:

0.00689

Hom.:

Bravo

AF:

0.00544

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 07, 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. -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	May 12, 2016	- -

Severe X-linked myotubular myopathy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.022

DANN

Benign

0.70

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