rs587783753

Positions:

• chrX-150596543-C-G
• chrX-150596543-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000252.3(MTM1):​c.109C>G​(p.Arg37Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000183 in 1,095,822 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000018 (0 hom. 1 hem.)
• Consequence: MTM1 NM_000252.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.84

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTM1	NM_000252.3	c.109C>G	p.Arg37Gly	missense_variant	3/15	ENST00000370396.7	NP_000243.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTM1	ENST00000370396.7	c.109C>G	p.Arg37Gly	missense_variant	3/15	1	NM_000252.3	ENSP00000359423.3

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.00000183 AC: 2 AN: 1095822 Hom.: 0 Cov.: 28 AF XY: 0.00000277 AC XY: 1 AN XY: 361570

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000238

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Uncertain	0.087	D
BayesDel_noAF	Benign	-0.11
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.79	D;.
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.96	D;D
M_CAP	Pathogenic	0.43	D
MetaRNN	Uncertain	0.65	D;D
MetaSVM	Uncertain	-0.020	T
MutationAssessor	Uncertain	2.1	M;.
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-2.3	N;D
REVEL	Pathogenic	0.66
Sift	Uncertain	0.023	D;T
Sift4G	Uncertain	0.039	D;T
Polyphen		0.90	P;.
Vest4		0.53
MutPred		0.68		Loss of helix (P = 0.1299);Loss of helix (P = 0.1299);
MVP		0.87
MPC		1.0
ClinPred		0.85	D
GERP RS		3.9
Varity_R		0.62
gMVP		0.88

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: rs587783753; hg19: chrX-149765007;