X-150568509-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The ENST00000685944.1(MTM1):c.-11+34C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.022 in 113,738 control chromosomes in the GnomAD database, including 29 homozygotes. There are 781 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 0.022 (29 hom., 780 hem., cov: 25)
  • Exomes 𝑓: 0.021 (0 hom. 1 hem.)
• Consequence: MTM1 ENST00000685944.1 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.86

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=-0.8).
• BP6: Variant X-150568509-C-T is Benign according to our data. Variant chrX-150568509-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1703406.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150568509-C-T is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.022 (2506/113690) while in subpopulation NFE AF= 0.0342 (1823/53354). AF 95% confidence interval is 0.0329. There are 29 homozygotes in gnomad4. There are 780 alleles in male gnomad4 subpopulation. Median coverage is 25. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 29 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTM1	XM_011531172.2	c.-11+5489C>T		intron_variant
MTM1	XM_047442132.1	c.-92+5489C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTM1	ENST00000685944.1	c.-11+34C>T		intron_variant				P1

Frequencies

GnomAD3 genomes AF: 0.0221 AC: 2506 AN: 113644 Hom.: 29 Cov.: 25 AF XY: 0.0218 AC XY: 779 AN XY: 35798

Gnomad AFR AF: 0.00408

Gnomad AMI AF: 0.0146

Gnomad AMR AF: 0.0205

Gnomad ASJ AF: 0.00863

Gnomad EAS AF: 0.000277

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.0395

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0342

Gnomad OTH AF: 0.0266

GnomAD4 exome AF: 0.0208 AC: 1 AN: 48 Hom.: 0 AF XY: 0.0556 AC XY: 1 AN XY: 18

Gnomad4 AFR exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.0238

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0220 AC: 2506 AN: 113690 Hom.: 29 Cov.: 25 AF XY: 0.0218 AC XY: 780 AN XY: 35854

Gnomad4 AFR AF: 0.00407

Gnomad4 AMR AF: 0.0205

Gnomad4 ASJ AF: 0.00863

Gnomad4 EAS AF: 0.000278

Gnomad4 SAS AF: 0.00208

Gnomad4 FIN AF: 0.0395

Gnomad4 NFE AF: 0.0342

Gnomad4 OTH AF: 0.0262

Alfa AF: 0.0281 Hom.: 150

Bravo AF: 0.0202

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 25, 2022

See Variant Classification Assertion Criteria. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	0.043
Dann	Benign	0.75

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs182709862; hg19: chrX-149736959;