Genetic Variant MTMR1:p.Lys236Gln (chrX-150730573-A-C) – 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.706A>C(p.Lys236Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000146 in 1,166,828 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 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 0.000089 ( 0 hom., 3 hem., cov: 23)

Exomes 𝑓: 0.0000066 ( 0 hom. 1 hem. )

Consequence

MTMR1
NM_001306144.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.25

Publications

1 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=0.16220653).

BS2

High Hemizygotes in GnomAd4 at 3 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.706A>C	p.Lys236Gln	missense	Exon 8 of 16	NP_001293073.1	F8WA39
MTMR1	NM_001353990.2		c.733A>C	p.Lys245Gln	missense	Exon 8 of 16	NP_001340919.1	E9PPP8
MTMR1	NM_003828.5		c.682A>C	p.Lys228Gln	missense	Exon 7 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.706A>C	p.Lys236Gln	missense	Exon 8 of 16	ENSP00000414178.2	F8WA39
MTMR1	ENST00000370390.7	TSL:1	c.682A>C	p.Lys228Gln	missense	Exon 7 of 16	ENSP00000359417.3	Q13613-1
MTMR1	ENST00000542156.5	TSL:1	c.682A>C	p.Lys228Gln	missense	Exon 7 of 10	ENSP00000445281.1	Q8NEC6

Frequencies

GnomAD3 genomes

AF:

0.0000889

AC:

AN:

112426

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000291

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000944

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000363

AC:

AN:

165236

AF XY:

0.0000371

show subpopulations

Gnomad AFR exome

AF:

0.000508

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000664

AC:

AN:

1054349

Hom.:

Cov.:

AF XY:

0.00000304

AC XY:

AN XY:

329185

show subpopulations

African (AFR)

AF:

0.000276

AC:

AN:

25387

American (AMR)

AF:

0.00

AC:

AN:

32782

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18522

East Asian (EAS)

AF:

0.00

AC:

AN:

29417

South Asian (SAS)

AF:

0.00

AC:

AN:

46650

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39107

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3957

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

814316

Other (OTH)

AF:

0.00

AC:

AN:

44211

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.400

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:

0.0000889

AC:

AN:

112479

Hom.:

Cov.:

AF XY:

0.0000866

AC XY:

AN XY:

34645

show subpopulations

African (AFR)

AF:

0.000290

AC:

AN:

31015

American (AMR)

AF:

0.0000943

AC:

AN:

10601

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2653

East Asian (EAS)

AF:

0.00

AC:

AN:

3605

South Asian (SAS)

AF:

0.00

AC:

AN:

2745

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6137

Middle Eastern (MID)

AF:

0.00

AC:

AN:

217

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53302

Other (OTH)

AF:

0.00

AC:

AN:

1519

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

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:

0.0000712

Hom.:

Bravo

AF:

0.0000945

ESP6500AA

AF:

0.000783

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000577

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

0.12

BayesDel_addAF

Pathogenic

0.35

BayesDel_noAF

Pathogenic

0.26

CADD

Uncertain

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.27

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.97

M_CAP

Uncertain

0.25

MetaRNN

Benign

0.16

MetaSVM

Uncertain

0.25

MutationAssessor

Benign

1.5

PhyloP100

9.2

PrimateAI

Benign

0.43

PROVEAN

Benign

-1.5

REVEL

Uncertain

0.53

Sift

Benign

0.094

Sift4G

Benign

0.21

Polyphen

0.023

Vest4

0.52

MVP

0.98

ClinPred

0.15

GERP RS

5.2

Varity_R

0.62

gMVP

0.63

Mutation Taster

=93/7

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