Genetic Variant MTMR1:p.Ala93Gly (chrX-150718626-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001306144.3(MTMR1):c.278C>G(p.Ala93Gly) variant causes a missense, splice region change. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000029 ( 0 hom., 1 hem., cov: 13)

Exomes 𝑓: 0.00038 ( 0 hom. 26 hem. )

Failed GnomAD Quality Control

Consequence

MTMR1
NM_001306144.3 missense, splice_region

Scores

Splicing: ADA: 0.5780

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.08

Publications

0 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.24816254).

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	HGVSp	Effect	Exon Rank	Protein	UniProt
MTMR1	NM_001306144.3	MANE Select	c.278C>G	p.Ala93Gly	missense splice_region	Exon 4 of 16	NP_001293073.1	F8WA39
MTMR1	NM_001353990.2		c.305C>G	p.Ala102Gly	missense splice_region	Exon 4 of 16	NP_001340919.1	E9PPP8
MTMR1	NM_003828.5		c.254C>G	p.Ala85Gly	missense splice_region	Exon 3 of 16	NP_003819.1	Q13613-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MTMR1	ENST00000445323.7	TSL:1 MANE Select	c.278C>G	p.Ala93Gly	missense splice_region	Exon 4 of 16	ENSP00000414178.2	F8WA39
MTMR1	ENST00000370390.7	TSL:1	c.254C>G	p.Ala85Gly	missense splice_region	Exon 3 of 16	ENSP00000359417.3	Q13613-1
MTMR1	ENST00000542156.5	TSL:1	c.254C>G	p.Ala85Gly	missense splice_region	Exon 3 of 10	ENSP00000445281.1	Q8NEC6

Frequencies

GnomAD3 genomes

AF:

0.0000292

AC:

AN:

68569

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00121

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000249

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000218

AC:

AN:

137301

AF XY:

0.0000250

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000457

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000378

AC:

113

AN:

299255

Hom.:

Cov.:

AF XY:

0.000254

AC XY:

AN XY:

102203

show subpopulations

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

African (AFR)

AF:

0.00

AC:

AN:

8001

American (AMR)

AF:

0.0000455

AC:

AN:

21955

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

8000

East Asian (EAS)

AF:

0.0000829

AC:

AN:

12063

South Asian (SAS)

AF:

0.000223

AC:

AN:

31368

European-Finnish (FIN)

AF:

0.00

AC:

AN:

21940

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1089

European-Non Finnish (NFE)

AF:

0.000562

AC:

102

AN:

181558

Other (OTH)

AF:

0.000151

AC:

AN:

13281

⚠️ 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: 0.346

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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

AF:

0.0000292

AC:

AN:

68595

Hom.:

Cov.:

AF XY:

0.0000791

AC XY:

AN XY:

12649

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

17104

American (AMR)

AF:

0.00

AC:

AN:

3960

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2040

East Asian (EAS)

AF:

0.00

AC:

AN:

1821

South Asian (SAS)

AF:

0.00121

AC:

AN:

827

European-Finnish (FIN)

AF:

0.00

AC:

AN:

1325

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0000249

AC:

AN:

40149

Other (OTH)

AF:

0.00

AC:

AN:

793

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00

Hom.:

ExAC

AF:

0.00000824

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Pathogenic

0.27

BayesDel_noAF

Pathogenic

0.28

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.32

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.63

M_CAP

Pathogenic

0.69

MetaRNN

Benign

0.25

MetaSVM

Uncertain

-0.19

MutationAssessor

Benign

1.9

PhyloP100

4.1

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-0.93

REVEL

Uncertain

0.50

Sift

Benign

0.41

Sift4G

Benign

0.28

Polyphen

0.0020

Vest4

0.40

MutPred

0.36

Loss of stability (P = 0.0334)

MVP

1.0

ClinPred

0.16

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.25

gMVP

0.60

Mutation Taster

=40/60

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.58

dbscSNV1_RF

Benign

0.43

SpliceAI score (max)

0.080

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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