X-150568649-G-C

Variant names:

• chrX-150568649-G-C
• rs1008075753
• NM_000252.3:c.-24G>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Moderate BS1

The NM_000252.3(MTM1):​c.-24G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000265 in 113,008 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. The gene MTM1 is included in the ClinGen Criteria Specification Registry.

• Frequency: Genomes: 𝑓 0.000027 (0 hom., 1 hem., cov: 26)
• Consequence: MTM1 NM_000252.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.235
• 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

Specifications for MTM1 are available in the ClinGen Criteria Specification Registry and recommended for reference when assigning criteria.

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.0000265 (3/113008) while in subpopulation AMR AF = 0.000276 (3/10870). AF 95% confidence interval is 0.0000748. There are 0 homozygotes in GnomAd4. There are 1 alleles in the male GnomAd4 subpopulation. Median coverage is 26. This position passed quality control check.

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.-24G>C		5_prime_UTR	Exon 1 of 15	NP_000243.1	Q13496-1
	MTM1	NM_001376908.1		c.-80G>C		5_prime_UTR	Exon 1 of 15	NP_001363837.1	Q13496-1
	MTM1	NM_001376906.1		c.-24G>C		5_prime_UTR	Exon 1 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.-24G>C		5_prime_UTR	Exon 1 of 15	ENSP00000359423.3	Q13496-1
	MTM1	ENST00000866458.1		c.-24G>C		5_prime_UTR	Exon 1 of 16	ENSP00000536517.1
	MTM1	ENST00000866460.1		c.-22G>C		5_prime_UTR	Exon 1 of 15	ENSP00000536519.1

Frequencies

GnomAD3 genomes AF: 0.0000265 AC: 3 AN: 113008 Hom.: 0 Cov.: 26

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000276

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

GnomAD4 exome Cov.: 0

GnomAD4 genome AF: 0.0000265 AC: 3 AN: 113008 Hom.: 0 Cov.: 26 AF XY: 0.0000284 AC XY: 1 AN XY: 35216

African (AFR) AF: 0.00 AC: 0 AN: 31207

American (AMR) AF: 0.000276 AC: 3 AN: 10870

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2659

East Asian (EAS) AF: 0.00 AC: 0 AN: 3562

South Asian (SAS) AF: 0.00 AC: 0 AN: 2839

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6235

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 236

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53195

Other (OTH) AF: 0.00 AC: 0 AN: 1523

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000680

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	16
DANN	Benign	0.84
PhyloP100		0.23
PromoterAI		-0.13	Neutral

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: rs1008075753; hg19: chrX-149737099;