rs185258809

Variant names:

• chrX-150658044-A-G
• rs185258809
• NM_000252.3:c.1260+17A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.607
• Publications: 0 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, Labcorp Genetics (formerly Invitae), Orphanet, ClinGen, G2P, Myriad Women’s Health, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 255621.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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 the male GnomAd4 subpopulation. Median coverage is 23. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 5 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.1260+17A>G		intron	N/A	NP_000243.1	Q13496-1
	MTM1	NM_001376908.1		c.1260+17A>G		intron	N/A	NP_001363837.1	Q13496-1
	MTM1	NM_001376906.1		c.1260+17A>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.1260+17A>G		intron	N/A	ENSP00000359423.3	Q13496-1
	MTM1	ENST00000689314.1		c.1305+17A>G		intron	N/A	ENSP00000510607.1	A0A8I5KZ76
	MTM1	ENST00000866458.1		c.1305+17A>G		intron	N/A	ENSP00000536517.1

Frequencies

GnomAD3 genomes AF: 0.00661 AC: 744 AN: 112551 Hom.: 5 Cov.: 23

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

GnomAD2 exomes AF: 0.00670 AC: 1169 AN: 174442 AF XY: 0.00651

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 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.: 39 Cov.: 22 AF XY: 0.00996 AC XY: 2836 AN XY: 284744

African (AFR) AF: 0.000741 AC: 18 AN: 24305

American (AMR) AF: 0.00289 AC: 101 AN: 34915

Ashkenazi Jewish (ASJ) AF: 0.00197 AC: 37 AN: 18750

East Asian (EAS) AF: 0.00 AC: 0 AN: 29744

South Asian (SAS) AF: 0.00175 AC: 90 AN: 51385

European-Finnish (FIN) AF: 0.0175 AC: 706 AN: 40240

Middle Eastern (MID) AF: 0.000770 AC: 3 AN: 3896

European-Non Finnish (NFE) AF: 0.0106 AC: 7991 AN: 756348

Other (OTH) AF: 0.00698 AC: 300 AN: 42965

GnomAD4 genome AF: 0.00661 AC: 744 AN: 112605 Hom.: 5 Cov.: 23 AF XY: 0.00682 AC XY: 237 AN XY: 34747

African (AFR) AF: 0.00145 AC: 45 AN: 31035

American (AMR) AF: 0.00197 AC: 21 AN: 10636

Ashkenazi Jewish (ASJ) AF: 0.00188 AC: 5 AN: 2659

East Asian (EAS) AF: 0.00 AC: 0 AN: 3613

South Asian (SAS) AF: 0.00 AC: 0 AN: 2767

European-Finnish (FIN) AF: 0.0232 AC: 142 AN: 6130

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 218

European-Non Finnish (NFE) AF: 0.00885 AC: 472 AN: 53326

Other (OTH) AF: 0.00716 AC: 11 AN: 1536

Alfa AF: 0.00689 Hom.: 58

Bravo AF: 0.00544

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	1	Severe X-linked myotubular myopathy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.022
DANN	Benign	0.70
PhyloP100		-0.61
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: rs185258809; hg19: chrX-149826517;