Genetic Variant MTMR1:p.Ala7Glu (chrX-150693550-C-A) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001306144.3(MTMR1):c.20C>A(p.Ala7Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000369 in 757,934 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 10 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000028 ( 0 hom., 0 hem., cov: 22)

Exomes 𝑓: 0.000038 ( 0 hom. 10 hem. )

Consequence

MTMR1
NM_001306144.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.186

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 -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.1914984).

BS2

High Hemizygotes in GnomAdExome4 at 10 gene

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.20C>A	p.Ala7Glu	missense	Exon 1 of 16	NP_001293073.1	F8WA39
MTMR1	NM_001353990.2		c.20C>A	p.Ala7Glu	missense	Exon 1 of 16	NP_001340919.1	E9PPP8
MTMR1	NM_003828.5		c.20C>A	p.Ala7Glu	missense	Exon 1 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.20C>A	p.Ala7Glu	missense	Exon 1 of 16	ENSP00000414178.2	F8WA39
MTMR1	ENST00000370390.7	TSL:1	c.20C>A	p.Ala7Glu	missense	Exon 1 of 16	ENSP00000359417.3	Q13613-1
MTMR1	ENST00000542156.5	TSL:1	c.20C>A	p.Ala7Glu	missense	Exon 1 of 10	ENSP00000445281.1	Q8NEC6

Frequencies

GnomAD3 genomes

AF:

0.0000278

AC:

AN:

107895

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:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000585

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000385

AC:

AN:

650039

Hom.:

Cov.:

AF XY:

0.0000510

AC XY:

AN XY:

196155

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

12574

American (AMR)

AF:

0.00

AC:

AN:

1097

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

4220

East Asian (EAS)

AF:

0.00

AC:

AN:

3359

South Asian (SAS)

AF:

0.00

AC:

AN:

12706

European-Finnish (FIN)

AF:

0.00

AC:

AN:

1328

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1147

European-Non Finnish (NFE)

AF:

0.0000406

AC:

AN:

591825

Other (OTH)

AF:

0.0000459

AC:

AN:

21783

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

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:

0.0000278

AC:

AN:

107895

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

32621

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30441

American (AMR)

AF:

0.00

AC:

AN:

10457

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2574

East Asian (EAS)

AF:

0.00

AC:

AN:

3426

South Asian (SAS)

AF:

0.00

AC:

AN:

2740

European-Finnish (FIN)

AF:

0.00

AC:

AN:

4554

Middle Eastern (MID)

AF:

0.00

AC:

AN:

233

European-Non Finnish (NFE)

AF:

0.0000585

AC:

AN:

51321

Other (OTH)

AF:

0.00

AC:

AN:

1477

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.0000712

Hom.:

Bravo

AF:

0.0000227

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

0.22

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Uncertain

-0.080

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.25

FATHMM_MKL

Benign

0.025

LIST_S2

Benign

0.53

M_CAP

Uncertain

0.099

MetaRNN

Benign

0.19

MetaSVM

Uncertain

0.014

MutationAssessor

Benign

1.1

PhyloP100

0.19

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

0.020

REVEL

Uncertain

0.38

Sift

Benign

0.34

Sift4G

Benign

0.28

Polyphen

0.032

Vest4

0.32

MutPred

0.23

Loss of catalytic residue at A7 (P = 0.3334)

MVP

0.93

ClinPred

0.53

GERP RS

3.0

PromoterAI

-0.013

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.0

Varity_R

0.12

gMVP

0.52

Mutation Taster

=87/13

polymorphism

(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

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