rs185258809

chrX-150658044-A-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

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. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 5 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTM1	NM_000252.3	c.1260+17A>G		intron_variant		ENST00000370396.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTM1	ENST00000370396.7	c.1260+17A>G		intron_variant		1	NM_000252.3	P1

Frequencies

GnomAD3 genomes AF: 0.00661 AC: 744 AN: 112551 Hom.: 5 Cov.: 23 AF XY: 0.00683 AC XY: 237 AN XY: 34683

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.: 6 AF XY: 0.00651 AC XY: 399 AN XY: 61330

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

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.: 5 Cov.: 23 AF XY: 0.00682 AC XY: 237 AN XY: 34747

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.: 58

Bravo AF: 0.00544

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

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	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Severe X-linked myotubular myopathy Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

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

Other links and lift over

dbSNP: rs185258809; hg19: chrX-149826517;