Genetic Variant MTMR1:c.277-41C>T (chrX-150718584-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong

The NM_001306144.3(MTMR1):c.277-41C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.92 ( 3494 hom., 3912 hem., cov: 0)

Exomes 𝑓: 0.78 ( 19137 hom. 49193 hem. )

Failed GnomAD Quality Control

Consequence

MTMR1
NM_001306144.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.00

Publications

2 publications found

Variant links:

Genes affected

MTMR1 (HGNC:7449): (myotubularin related protein 1) This gene encodes a member of the myotubularin related family of proteins. Members of this family contain the consensus sequence for the active site of protein tyrosine phosphatases. Alternatively spliced variants have been described but their biological validity has not been determined. [provided by RefSeq, Jul 2008]

MTMR1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant X-150718584-C-T is Benign according to our data. Variant chrX-150718584-C-T is described in ClinVar as Benign. ClinVar VariationId is 1231508.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001306144.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MTMR1	NM_001306144.3	MANE Select	c.277-41C>T	intron	N/A	NP_001293073.1	F8WA39
MTMR1	NM_001353990.2		c.304-41C>T	intron	N/A	NP_001340919.1	E9PPP8
MTMR1	NM_003828.5		c.253-41C>T	intron	N/A	NP_003819.1	Q13613-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MTMR1	ENST00000445323.7	TSL:1 MANE Select	c.277-41C>T	intron	N/A	ENSP00000414178.2	F8WA39
MTMR1	ENST00000370390.7	TSL:1	c.253-41C>T	intron	N/A	ENSP00000359417.3	Q13613-1
MTMR1	ENST00000542156.5	TSL:1	c.253-41C>T	intron	N/A	ENSP00000445281.1	Q8NEC6

Frequencies

GnomAD3 genomes

AF:

0.915

AC:

11443

AN:

12502

Hom.:

3493

Cov.:

show subpopulations

Gnomad AFR

AF:

0.938

Gnomad AMI

AF:

0.845

Gnomad AMR

AF:

0.895

Gnomad ASJ

AF:

0.902

Gnomad EAS

AF:

0.931

Gnomad SAS

AF:

0.970

Gnomad FIN

AF:

0.981

Gnomad MID

AF:

1.00

Gnomad NFE

AF:

0.898

Gnomad OTH

AF:

0.903

GnomAD2 exomes

AF:

0.929

AC:

62087

AN:

66838

AF XY:

0.978

show subpopulations

Gnomad AFR exome

AF:

0.699

Gnomad AMR exome

AF:

0.891

Gnomad ASJ exome

AF:

0.969

Gnomad EAS exome

AF:

0.929

Gnomad FIN exome

AF:

0.992

Gnomad NFE exome

AF:

0.963

Gnomad OTH exome

AF:

0.917

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.781

AC:

91708

AN:

117434

Hom.:

19137

Cov.:

AF XY:

0.957

AC XY:

49193

AN XY:

51406

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.822

AC:

2140

AN:

2603

American (AMR)

AF:

0.964

AC:

5452

AN:

5657

Ashkenazi Jewish (ASJ)

AF:

0.915

AC:

2595

AN:

2835

East Asian (EAS)

AF:

0.913

AC:

4625

AN:

5067

South Asian (SAS)

AF:

0.960

AC:

11923

AN:

12418

European-Finnish (FIN)

AF:

0.972

AC:

7681

AN:

7901

Middle Eastern (MID)

AF:

0.911

AC:

347

AN:

381

European-Non Finnish (NFE)

AF:

0.701

AC:

53307

AN:

75992

Other (OTH)

AF:

0.794

AC:

3638

AN:

4580

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.334

Heterozygous variant carriers

284

567

851

1134

1418

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1122

2244

3366

4488

5610

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.915

AC:

11450

AN:

12508

Hom.:

3494

Cov.:

AF XY:

0.995

AC XY:

3912

AN XY:

3930

show subpopulations

African (AFR)

AF:

0.938

AC:

3405

AN:

3631

American (AMR)

AF:

0.895

AC:

675

AN:

754

Ashkenazi Jewish (ASJ)

AF:

0.902

AC:

332

AN:

368

East Asian (EAS)

AF:

0.931

AC:

362

AN:

389

South Asian (SAS)

AF:

0.970

AC:

289

AN:

298

European-Finnish (FIN)

AF:

0.981

AC:

461

AN:

470

Middle Eastern (MID)

AF:

1.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.898

AC:

5697

AN:

6342

Other (OTH)

AF:

0.908

AC:

138

AN:

152

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.539

Heterozygous variant carriers

123

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

220

330

440

550

<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:

0.861

Hom.:

8507

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

2.8

(source)

DANN

Benign

0.42

PhyloP100

0.0

Mutation Taster

=14/86

disease causing

(source)

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

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over