chrX-150592665-G-A

Variant names:

• chrX-150592665-G-A
• rs148455726
• NM_000252.3:c.51G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BS1 BS2

The NM_000252.3(MTM1):​c.51G>A​(p.Glu17Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000685 in 1,167,674 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000027 (0 hom., 2 hem., cov: 23)
  • Exomes 𝑓: 0.0000047 (0 hom. 2 hem.)
• Consequence: MTM1 NM_000252.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.155
• Publications: 2 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP6: Variant X-150592665-G-A is Benign according to our data. Variant chrX-150592665-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1125967.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.155 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAdExome4 allele frequency = 0.00000473 (5/1055993) while in subpopulation AFR AF = 0.000195 (5/25614). AF 95% confidence interval is 0.000076. There are 0 homozygotes in GnomAdExome4. There are 2 alleles in the male GnomAdExome4 subpopulation. Median coverage is 24. This position passed quality control check.
• BS2: High Hemizygotes in GnomAd4 at 2 XL gene

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.51G>A	p.Glu17Glu	synonymous	Exon 2 of 15	NP_000243.1	Q13496-1
	MTM1	NM_001376908.1		c.51G>A	p.Glu17Glu	synonymous	Exon 2 of 15	NP_001363837.1	Q13496-1
	MTM1	NM_001376906.1		c.51G>A	p.Glu17Glu	synonymous	Exon 2 of 15	NP_001363835.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTM1	ENST00000370396.7	TSL:1 MANE Select	c.51G>A	p.Glu17Glu	synonymous	Exon 2 of 15	ENSP00000359423.3	Q13496-1
	MTM1	ENST00000689314.1		c.51G>A	p.Glu17Glu	synonymous	Exon 2 of 16	ENSP00000510607.1	A0A8I5KZ76
	MTM1	ENST00000866458.1		c.51G>A	p.Glu17Glu	synonymous	Exon 2 of 16	ENSP00000536517.1

Frequencies

GnomAD3 genomes AF: 0.0000179 AC: 2 AN: 111626 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.0000652

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

GnomAD2 exomes AF: 0.0000110 AC: 2 AN: 182648 AF XY: 0.00

Gnomad AFR exome AF: 0.000152

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000473 AC: 5 AN: 1055993 Hom.: 0 Cov.: 24 AF XY: 0.00000612 AC XY: 2 AN XY: 326831

African (AFR) AF: 0.000195 AC: 5 AN: 25614

American (AMR) AF: 0.00 AC: 0 AN: 35150

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19092

East Asian (EAS) AF: 0.00 AC: 0 AN: 30030

South Asian (SAS) AF: 0.00 AC: 0 AN: 53162

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40041

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4016

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 804205

Other (OTH) AF: 0.00 AC: 0 AN: 44683

GnomAD4 genome AF: 0.0000269 AC: 3 AN: 111681 Hom.: 0 Cov.: 23 AF XY: 0.0000590 AC XY: 2 AN XY: 33903

African (AFR) AF: 0.0000976 AC: 3 AN: 30751

American (AMR) AF: 0.00 AC: 0 AN: 10540

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2645

East Asian (EAS) AF: 0.00 AC: 0 AN: 3582

South Asian (SAS) AF: 0.00 AC: 0 AN: 2701

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5933

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 217

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53107

Other (OTH) AF: 0.00 AC: 0 AN: 1520

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000416

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Severe X-linked myotubular myopathy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	3.8
DANN	Benign	0.57
PhyloP100		-0.15

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: rs148455726; hg19: chrX-149761127; COSMIC: COSV100080374;