Variant 17-58507147-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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. 15/20 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

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 made for transcript

Verdict is Benign. Variant got -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/exons	MANE	UniProt
MTMR4	NM_001378067.1 linkuse as main transcript	c.880A>G	p.Ser294Gly	missense_variant	8/18	ENST00000682306.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
MTMR4	ENST00000682306.1 linkuse as main transcript	c.880A>G	p.Ser294Gly	missense_variant	8/18		NM_001378067.1	A1
MTMR4	ENST00000323456.9 linkuse as main transcript	c.838A>G	p.Ser280Gly	missense_variant	9/19	1		P4
MTMR4	ENST00000579925.5 linkuse as main transcript	c.838A>G	p.Ser280Gly	missense_variant	9/18	5

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

GnomAD3 exomes

AF:

0.240

AC:

60273

AN:

251214

Hom.:

8256

AF XY:

0.244

AC XY:

33157

AN XY:

135812

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 SAS exome

AF:

0.345

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

Gnomad4 AFR exome

AF:

0.443

Gnomad4 AMR exome

AF:

0.137

Gnomad4 ASJ exome

AF:

0.303

Gnomad4 EAS exome

AF:

0.305

Gnomad4 SAS exome

AF:

0.348

Gnomad4 FIN exome

AF:

0.215

Gnomad4 NFE exome

AF:

0.192

Gnomad4 OTH exome

AF:

0.245

GnomAD4 genome

AF:

0.274

AC:

41671

AN:

152008

Hom.:

6645

Cov.:

AF XY:

0.274

AC XY:

20392

AN XY:

74306

show subpopulations

Gnomad4 AFR

AF:

0.429

Gnomad4 AMR

AF:

0.181

Gnomad4 ASJ

AF:

0.305

Gnomad4 EAS

AF:

0.329

Gnomad4 SAS

AF:

0.363

Gnomad4 FIN

AF:

0.219

Gnomad4 NFE

AF:

0.199

Gnomad4 OTH

AF:

0.264

Alfa

AF:

0.216

Hom.:

6550

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

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

MutationTaster

Benign

1.0

P;P

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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over