rs2138413

Variant names:

• chrX-150592277-A-G
• rs2138413
• NM_000252.3:c.-10-328A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000252.3(MTM1):​c.-10-328A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.277 in 110,945 control chromosomes in the GnomAD database, including 3,365 homozygotes. There are 9,128 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.28 (3365 hom., 9128 hem., cov: 23)
• Consequence: MTM1 NM_000252.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0940
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• X-linked myotubular myopathy

  Inheritance: XL Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Genomics England PanelApp, ClinGen, Labcorp Genetics (formerly Invitae), Myriad Women’s Health, Ambry Genetics, G2P, Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant X-150592277-A-G is Benign according to our data. Variant chrX-150592277-A-G is described in ClinVar as Benign. ClinVar VariationId is 1251658.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.491 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000252.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTM1	NM_000252.3	MANE Select	c.-10-328A>G		intron	N/A	NP_000243.1	Q13496-1
	MTM1	NM_001376908.1		c.-10-328A>G		intron	N/A	NP_001363837.1	Q13496-1
	MTM1	NM_001376906.1		c.-10-328A>G		intron	N/A	NP_001363835.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTM1	ENST00000370396.7	TSL:1 MANE Select	c.-10-328A>G		intron	N/A	ENSP00000359423.3	Q13496-1
	MTM1	ENST00000866479.1		c.-338A>G		5_prime_UTR	Exon 1 of 14	ENSP00000536538.1
	MTM1	ENST00000689314.1		c.-10-328A>G		intron	N/A	ENSP00000510607.1	A0A8I5KZ76

Frequencies

GnomAD3 genomes AF: 0.277 AC: 30697 AN: 110890 Hom.: 3368 Cov.: 23

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.445

Gnomad AMR AF: 0.417

Gnomad ASJ AF: 0.382

Gnomad EAS AF: 0.239

Gnomad SAS AF: 0.513

Gnomad FIN AF: 0.256

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.310

Gnomad OTH AF: 0.324

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.277 AC: 30686 AN: 110945 Hom.: 3365 Cov.: 23 AF XY: 0.275 AC XY: 9128 AN XY: 33173

African (AFR) AF: 0.142 AC: 4339 AN: 30578

American (AMR) AF: 0.417 AC: 4336 AN: 10396

Ashkenazi Jewish (ASJ) AF: 0.382 AC: 1006 AN: 2633

East Asian (EAS) AF: 0.239 AC: 844 AN: 3530

South Asian (SAS) AF: 0.513 AC: 1358 AN: 2645

European-Finnish (FIN) AF: 0.256 AC: 1514 AN: 5916

Middle Eastern (MID) AF: 0.486 AC: 105 AN: 216

European-Non Finnish (NFE) AF: 0.310 AC: 16398 AN: 52850

Other (OTH) AF: 0.323 AC: 488 AN: 1512

Alfa AF: 0.294 Hom.: 2816

Bravo AF: 0.282

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.5
DANN	Benign	0.62
PhyloP100		-0.094
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2138413; hg19: chrX-149760739;