dbSNP rs946865351: MTM1:p.Ala2Ala (chrX-150592620-T-C) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_000252.3(MTM1):c.6T>C(p.Ala2Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. A2A) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 0.0 ( 0 hom. 0 hem. )

Failed GnomAD Quality Control

Consequence

MTM1
NM_000252.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0900

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, ClinGen, Labcorp Genetics (formerly Invitae), Myriad Women’s Health, Ambry Genetics, G2P, Orphanet

MTM1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.65).

BP6

Variant X-150592620-T-C is Benign according to our data. Variant chrX-150592620-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2806721.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.09 with no splicing effect.

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MTM1	NM_000252.3	MANE Select	c.6T>C	p.Ala2Ala	synonymous	Exon 2 of 15	NP_000243.1	Q13496-1
MTM1	NM_001376908.1		c.6T>C	p.Ala2Ala	synonymous	Exon 2 of 15	NP_001363837.1	Q13496-1
MTM1	NM_001376906.1		c.6T>C	p.Ala2Ala	synonymous	Exon 2 of 15	NP_001363835.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MTM1	ENST00000370396.7	TSL:1 MANE Select	c.6T>C	p.Ala2Ala	synonymous	Exon 2 of 15	ENSP00000359423.3	Q13496-1
MTM1	ENST00000689314.1		c.6T>C	p.Ala2Ala	synonymous	Exon 2 of 16	ENSP00000510607.1	A0A8I5KZ76
MTM1	ENST00000866458.1		c.6T>C	p.Ala2Ala	synonymous	Exon 2 of 16	ENSP00000536517.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1085076

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

351858

African (AFR)

AF:

0.00

AC:

AN:

26177

American (AMR)

AF:

0.00

AC:

AN:

35176

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19298

East Asian (EAS)

AF:

0.00

AC:

AN:

30133

South Asian (SAS)

AF:

0.00

AC:

AN:

53871

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40148

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4099

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

830513

Other (OTH)

AF:

0.00

AC:

AN:

45661

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions as Germline

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Severe X-linked myotubular myopathy (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

8.6

(source)

DANN

Benign

0.71

PhyloP100

0.090

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over