rs111468862

Variant names:

• chrX-150592357-C-T
• rs111468862
• NM_000252.3:c.-10-248C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_000252.3(MTM1):​c.-10-248C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0067 in 110,880 control chromosomes in the GnomAD database, including 6 homozygotes. There are 186 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.0067 (6 hom., 186 hem., cov: 22)
• Consequence: MTM1 NM_000252.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0280
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant X-150592357-C-T is Benign according to our data. Variant chrX-150592357-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1209394.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0067 (743/110880) while in subpopulation AFR AF = 0.0232 (705/30448). AF 95% confidence interval is 0.0217. There are 6 homozygotes in GnomAd4. There are 186 alleles in the male GnomAd4 subpopulation. Median coverage is 22. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 6 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.-10-248C>T		intron	N/A	NP_000243.1	Q13496-1
	MTM1	NM_001376908.1		c.-10-248C>T		intron	N/A	NP_001363837.1	Q13496-1
	MTM1	NM_001376906.1		c.-10-248C>T		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.-10-248C>T		intron	N/A	ENSP00000359423.3	Q13496-1
	MTM1	ENST00000866479.1		c.-258C>T		5_prime_UTR	Exon 1 of 14	ENSP00000536538.1
	MTM1	ENST00000689314.1		c.-10-248C>T		intron	N/A	ENSP00000510607.1	A0A8I5KZ76

Frequencies

GnomAD3 genomes AF: 0.00669 AC: 741 AN: 110828 Hom.: 6 Cov.: 22

Gnomad AFR AF: 0.0231

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00307

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: 0.0000189

Gnomad OTH AF: 0.00339

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.00670 AC: 743 AN: 110880 Hom.: 6 Cov.: 22 AF XY: 0.00562 AC XY: 186 AN XY: 33122

African (AFR) AF: 0.0232 AC: 705 AN: 30448

American (AMR) AF: 0.00307 AC: 32 AN: 10428

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2617

East Asian (EAS) AF: 0.00 AC: 0 AN: 3530

South Asian (SAS) AF: 0.00 AC: 0 AN: 2620

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5915

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 217

European-Non Finnish (NFE) AF: 0.0000189 AC: 1 AN: 52924

Other (OTH) AF: 0.00334 AC: 5 AN: 1495

Alfa AF: 0.00555 Hom.: 20

Bravo AF: 0.00766

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.1
DANN	Benign	0.74
PhyloP100		-0.028
Mutation Taster		=100/0	polymorphism

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: rs111468862; hg19: chrX-149760819;