Genetic Variant MTMR3:p.Thr697Ala (chr22-30019748-A-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_021090.4(MTMR3):c.2089A>G(p.Thr697Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

MTMR3
NM_021090.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.85

Publications

0 publications found

Variant links:

Genes affected

MTMR3 (HGNC:7451): (myotubularin related protein 3) This gene encodes a member of the myotubularin dual specificity protein phosphatase gene family. The encoded protein is structurally similar to myotubularin but in addition contains a FYVE domain and an N-terminal PH-GRAM domain. The protein can self-associate and also form heteromers with another myotubularin related protein. The protein binds to phosphoinositide lipids through the PH-GRAM domain, and can hydrolyze phosphatidylinositol(3)-phosphate and phosphatidylinositol(3,5)-biphosphate in vitro. The encoded protein has been observed to have a perinuclear, possibly membrane-bound, distribution in cells, but it has also been found free in the cytoplasm. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

MTMR3 links:

HORMAD2-AS1 (HGNC:50729): (HORMAD2 and MTMR3 antisense RNA 1)

HORMAD2-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.21997148).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021090.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MTMR3	NM_021090.4	MANE Select	c.2089A>G	p.Thr697Ala	missense	Exon 17 of 20	NP_066576.1	Q13615-1
MTMR3	NM_153050.3		c.2089A>G	p.Thr697Ala	missense	Exon 17 of 20	NP_694690.1	Q13615-2
MTMR3	NM_153051.3		c.2089A>G	p.Thr697Ala	missense	Exon 17 of 19	NP_694691.1	Q13615-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MTMR3	ENST00000401950.7	TSL:1 MANE Select	c.2089A>G	p.Thr697Ala	missense	Exon 17 of 20	ENSP00000384651.3	Q13615-1
MTMR3	ENST00000351488.7	TSL:1	c.2089A>G	p.Thr697Ala	missense	Exon 17 of 19	ENSP00000307271.6	Q13615-3
MTMR3	ENST00000956491.1		c.2191A>G	p.Thr731Ala	missense	Exon 18 of 21	ENSP00000626550.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

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

0.091

BayesDel_addAF

Uncertain

0.047

BayesDel_noAF

Benign

-0.17

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.35

Eigen

Benign

-0.33

Eigen_PC

Benign

-0.21

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.077

MetaRNN

Benign

0.22

MetaSVM

Benign

-0.33

MutationAssessor

Benign

1.8

PhyloP100

3.8

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-1.8

REVEL

Benign

0.28

Sift

Benign

0.13

Sift4G

Benign

0.78

Polyphen

0.57

Vest4

0.39

MutPred

0.15

Loss of phosphorylation at T697 (P = 0.0305)

MVP

0.84

MPC

0.16

ClinPred

0.43

GERP RS

3.7

Varity_R

0.071

gMVP

0.31

Mutation Taster

=72/28

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over