Variant 17-58494951-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001378067.1(MTMR4):c.3233T>C(p.Met1078Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000136 in 1,614,070 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

MTMR4
NM_001378067.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.72

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.10125744).

BS2

High AC in GnomAd4 at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTMR4	NM_001378067.1 linkuse as main transcript	c.3233T>C	p.Met1078Thr	missense_variant	15/18	ENST00000682306.1	NP_001364996.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MTMR4	ENST00000682306.1 linkuse as main transcript	c.3233T>C	p.Met1078Thr	missense_variant	15/18		NM_001378067.1	ENSP00000507664.1	A0A804HJV7
MTMR4	ENST00000323456.9 linkuse as main transcript	c.3191T>C	p.Met1064Thr	missense_variant	16/19	1		ENSP00000325285.5	Q9NYA4
MTMR4	ENST00000579925.5 linkuse as main transcript	c.3020T>C	p.Met1007Thr	missense_variant	15/18	5		ENSP00000464067.1	J3QR65

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

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:

0.000957

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

250906

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135602

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000327

GnomAD4 exome

AF:

0.00000958

AC:

AN:

1461780

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

727200

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000201

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000828

GnomAD4 genome

AF:

0.0000525

AC:

AN:

152290

Hom.:

Cov.:

AF XY:

0.0000671

AC XY:

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000947

Bravo

AF:

0.000212

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 03, 2024

The c.3191T>C (p.M1064T) alteration is located in exon 16 (coding exon 15) of the MTMR4 gene. This alteration results from a T to C substitution at nucleotide position 3191, causing the methionine (M) at amino acid position 1064 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.045

BayesDel_noAF

Benign

-0.13

CADD

Benign

DANN

Benign

0.62

DEOGEN2

Benign

0.24

T;T

Eigen

Benign

-0.17

Eigen_PC

Benign

0.018

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.83

T;T

M_CAP

Benign

0.064

MetaRNN

Benign

0.10

T;T

MetaSVM

Benign

-0.35

MutationAssessor

Benign

1.0

.;L

MutationTaster

Benign

0.80

N;N

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-1.0

.;N

REVEL

Benign

0.22

Sift

Benign

0.18

.;T

Sift4G

Benign

0.74

T;T

Polyphen

0.0010

.;B

Vest4

0.45

MVP

0.35

MPC

0.35

ClinPred

0.26

GERP RS

4.6

Varity_R

0.070

gMVP

0.087

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over