X-150592277-A-G

Variant summary

Our verdict is Benign. Variant got -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

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 -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTM1	NM_000252.3	c.-10-328A>G		intron_variant		ENST00000370396.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTM1	ENST00000370396.7	c.-10-328A>G		intron_variant		1	NM_000252.3	P1

Frequencies

GnomAD3 genomes AF: 0.277 AC: 30697 AN: 110890 Hom.: 3368 Cov.: 23 AF XY: 0.276 AC XY: 9127 AN XY: 33108

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

Gnomad4 AFR AF: 0.142

Gnomad4 AMR AF: 0.417

Gnomad4 ASJ AF: 0.382

Gnomad4 EAS AF: 0.239

Gnomad4 SAS AF: 0.513

Gnomad4 FIN AF: 0.256

Gnomad4 NFE AF: 0.310

Gnomad4 OTH AF: 0.323

Alfa AF: 0.294 Hom.: 2816

Bravo AF: 0.282

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	5.5
Dann	Benign	0.62

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: rs2138413; hg19: chrX-149760739;