rs192433136

Variant names:

• chrX-150568713-C-T
• rs192433136
• NM_000252.3:c.-11+51C>T

Variant summary

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

The NM_001376908.1(MTM1):​c.-16C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00526 in 113,206 control chromosomes in the GnomAD database, including 8 homozygotes. There are 149 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 0.0053 (8 hom., 149 hem., cov: 26)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: MTM1 NM_001376908.1 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.05
• 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, ClinGen, Labcorp Genetics (formerly Invitae), Myriad Women’s Health, Ambry Genetics, G2P, Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant X-150568713-C-T is Benign according to our data. Variant chrX-150568713-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1691156.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00526 (595/113206) while in subpopulation AFR AF = 0.0181 (568/31301). AF 95% confidence interval is 0.0169. There are 8 homozygotes in GnomAd4. There are 149 alleles in the male GnomAd4 subpopulation. Median coverage is 26. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 8 XL gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001376908.1. 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.-11+51C>T		intron	N/A	NP_000243.1	Q13496-1
	MTM1	NM_001376908.1		c.-16C>T		5_prime_UTR	Exon 1 of 15	NP_001363837.1	Q13496-1
	MTM1	NM_001376906.1		c.-11+51C>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.-11+51C>T		intron	N/A	ENSP00000359423.3	Q13496-1
	MTM1	ENST00000866469.1		c.-13C>T		splice_region	Exon 1 of 15	ENSP00000536528.1
	MTM1	ENST00000689694.1		c.-16C>T		5_prime_UTR	Exon 1 of 15	ENSP00000508718.1	Q13496-1

Frequencies

GnomAD3 genomes AF: 0.00520 AC: 588 AN: 113160 Hom.: 7 Cov.: 26

Gnomad AFR AF: 0.0180

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00156

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00426

Gnomad NFE AF: 0.0000188

Gnomad OTH AF: 0.00522

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 83 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 39

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 1

South Asian (SAS) AF: 0.00 AC: 0 AN: 1

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 79

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.00526 AC: 595 AN: 113206 Hom.: 8 Cov.: 26 AF XY: 0.00421 AC XY: 149 AN XY: 35386

African (AFR) AF: 0.0181 AC: 568 AN: 31301

American (AMR) AF: 0.00156 AC: 17 AN: 10896

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 3550

South Asian (SAS) AF: 0.00 AC: 0 AN: 2840

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6271

Middle Eastern (MID) AF: 0.00467 AC: 1 AN: 214

European-Non Finnish (NFE) AF: 0.0000188 AC: 1 AN: 53241

Other (OTH) AF: 0.00515 AC: 8 AN: 1553

Alfa AF: 0.00470 Hom.: 14

Bravo AF: 0.00588

ClinVar

ClinVar submissions as Germline

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	-0.92
CADD	Benign	4.2
DANN	Benign	0.86
PhyloP100		-1.1
PromoterAI		0.11	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs192433136; hg19: chrX-149737163;