Genetic Variant MTM1:c.-11+34C>T (chrX-150568509-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

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

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.86

Publications

0 publications found

Variant links:

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

MTM1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 1703406.Status of the report is criteria_provided_single_submitter, 1 stars.

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 the male GnomAd4 subpopulation. Median coverage is 25. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 29 XL gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000685944.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MTM1	NM_000252.3	MANE Select	c.-164C>T	upstream_gene	N/A	NP_000243.1	Q13496-1
MTM1	NM_001376908.1		c.-220C>T	upstream_gene	N/A	NP_001363837.1	Q13496-1
MTM1	NM_001376906.1		c.-164C>T	upstream_gene	N/A	NP_001363835.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MTM1	ENST00000685944.1		c.-11+34C>T	intron	N/A	ENSP00000509266.1	Q13496-1
MTM1	ENST00000370396.7	TSL:1 MANE Select	c.-164C>T	upstream_gene	N/A	ENSP00000359423.3	Q13496-1
MTM1	ENST00000689314.1		c.-368C>T	upstream_gene	N/A	ENSP00000510607.1	A0A8I5KZ76

Frequencies

GnomAD3 genomes

AF:

0.0221

AC:

2506

AN:

113644

Hom.:

Cov.:

show subpopulations

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:

AN:

Hom.:

AF XY:

0.0556

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0238

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

GnomAD4 genome

AF:

0.0220

AC:

2506

AN:

113690

Hom.:

Cov.:

AF XY:

0.0218

AC XY:

780

AN XY:

35854

show subpopulations

African (AFR)

AF:

0.00407

AC:

128

AN:

31464

American (AMR)

AF:

0.0205

AC:

224

AN:

10930

Ashkenazi Jewish (ASJ)

AF:

0.00863

AC:

AN:

2664

East Asian (EAS)

AF:

0.000278

AC:

AN:

3595

South Asian (SAS)

AF:

0.00208

AC:

AN:

2890

European-Finnish (FIN)

AF:

0.0395

AC:

250

AN:

6328

Middle Eastern (MID)

AF:

0.00

AC:

AN:

217

European-Non Finnish (NFE)

AF:

0.0342

AC:

1823

AN:

53354

Other (OTH)

AF:

0.0262

AC:

AN:

1563

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

190

286

381

476

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

160

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0281

Hom.:

150

Bravo

AF:

0.0202

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.043

(source)

DANN

Benign

0.75

PhyloP100

-1.9

PromoterAI

-0.049

Neutral

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over