Genetic Variant MTMR4:p.Ser294Gly (chr17-58507147-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001378067.1(MTMR4):c.880A>G(p.Ser294Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 1,613,758 control chromosomes in the GnomAD database, including 43,031 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.27 ( 6645 hom., cov: 31)

Exomes 𝑓: 0.21 ( 36386 hom. )

Consequence

MTMR4
NM_001378067.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.07

Publications

40 publications found

Variant links:

Genes affected

MTMR4 (HGNC:7452): (myotubularin related protein 4) Enables protein phosphatase binding activity. Involved in regulation of phosphatidylinositol dephosphorylation. Located in endosome. [provided by Alliance of Genome Resources, Apr 2022]

MTMR4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.003486067).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.424 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTMR4	NM_001378067.1 link	c.880A>G	p.Ser294Gly	missense_variant	Exon 8 of 18	ENST00000682306.1	NP_001364996.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MTMR4	ENST00000682306.1 link	c.880A>G	p.Ser294Gly	missense_variant	Exon 8 of 18		NM_001378067.1	ENSP00000507664.1	A0A804HJV7
MTMR4	ENST00000323456.9 link	c.838A>G	p.Ser280Gly	missense_variant	Exon 9 of 19	1		ENSP00000325285.5	Q9NYA4
MTMR4	ENST00000579925.5 link	c.838A>G	p.Ser280Gly	missense_variant	Exon 9 of 18	5		ENSP00000464067.1	J3QR65

Frequencies

GnomAD3 genomes

AF:

0.274

AC:

41598

AN:

151888

Hom.:

6618

Cov.:

show subpopulations

Gnomad AFR

AF:

0.429

Gnomad AMI

AF:

0.0844

Gnomad AMR

AF:

0.181

Gnomad ASJ

AF:

0.305

Gnomad EAS

AF:

0.329

Gnomad SAS

AF:

0.363

Gnomad FIN

AF:

0.219

Gnomad MID

AF:

0.358

Gnomad NFE

AF:

0.200

Gnomad OTH

AF:

0.256

GnomAD2 exomes

AF:

0.240

AC:

60273

AN:

251214

AF XY:

0.244

show subpopulations

Gnomad AFR exome

AF:

0.431

Gnomad AMR exome

AF:

0.130

Gnomad ASJ exome

AF:

0.302

Gnomad EAS exome

AF:

0.327

Gnomad FIN exome

AF:

0.224

Gnomad NFE exome

AF:

0.201

Gnomad OTH exome

AF:

0.239

GnomAD4 exome

AF:

0.214

AC:

312807

AN:

1461750

Hom.:

36386

Cov.:

AF XY:

0.219

AC XY:

159332

AN XY:

727210

show subpopulations

African (AFR)

AF:

0.443

AC:

14815

AN:

33470

American (AMR)

AF:

0.137

AC:

6126

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.303

AC:

7910

AN:

26134

East Asian (EAS)

AF:

0.305

AC:

12118

AN:

39698

South Asian (SAS)

AF:

0.348

AC:

30057

AN:

86252

European-Finnish (FIN)

AF:

0.215

AC:

11493

AN:

53414

Middle Eastern (MID)

AF:

0.341

AC:

1968

AN:

5764

European-Non Finnish (NFE)

AF:

0.192

AC:

213520

AN:

1111904

Other (OTH)

AF:

0.245

AC:

14800

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

14106

28212

42319

56425

70531

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7620

15240

22860

30480

38100

<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:

0.274

AC:

41671

AN:

152008

Hom.:

6645

Cov.:

AF XY:

0.274

AC XY:

20392

AN XY:

74306

show subpopulations

African (AFR)

AF:

0.429

AC:

17791

AN:

41426

American (AMR)

AF:

0.181

AC:

2760

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.305

AC:

1058

AN:

3470

East Asian (EAS)

AF:

0.329

AC:

1693

AN:

5152

South Asian (SAS)

AF:

0.363

AC:

1750

AN:

4816

European-Finnish (FIN)

AF:

0.219

AC:

2317

AN:

10568

Middle Eastern (MID)

AF:

0.364

AC:

107

AN:

294

European-Non Finnish (NFE)

AF:

0.199

AC:

13561

AN:

67980

Other (OTH)

AF:

0.264

AC:

557

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1455

2909

4364

5818

7273

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

434

868

1302

1736

2170

<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:

0.227

Hom.:

14271

Bravo

AF:

0.275

TwinsUK

AF:

0.196

AC:

728

ALSPAC

AF:

0.189

AC:

729

ESP6500AA

AF:

0.418

AC:

1840

ESP6500EA

AF:

0.203

AC:

1750

ExAC

AF:

0.246

AC:

29851

Asia WGS

AF:

0.356

AC:

1235

AN:

3478

EpiCase

AF:

0.210

EpiControl

AF:

0.212

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.058

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.30

CADD

Benign

(source)

DANN

Benign

0.82

DEOGEN2

Uncertain

0.47

T;T

Eigen

Benign

-0.50

Eigen_PC

Benign

-0.29

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.71

T;T

MetaRNN

Benign

0.0035

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.66

.;N

PhyloP100

1.1

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.35

.;N

REVEL

Benign

0.28

Sift

Benign

0.52

.;T

Sift4G

Benign

0.39

T;T

Polyphen

0.0

.;B

Vest4

0.051

MPC

0.59

ClinPred

0.0041

GERP RS

4.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.090

gMVP

0.49

Mutation Taster

=97/3

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over