Variant 22-30007952-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_021090.4(MTMR3):c.929A>G(p.Gln310Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000327 in 1,613,672 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00033 ( 0 hom. )

Consequence

MTMR3
NM_021090.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.95

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:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10464987).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
MTMR3	NM_021090.4 linkuse as main transcript	c.929A>G	p.Gln310Arg	missense_variant	11/20	ENST00000401950.7
MTMR3	NM_153050.3 linkuse as main transcript	c.929A>G	p.Gln310Arg	missense_variant	11/20
MTMR3	NM_153051.3 linkuse as main transcript	c.929A>G	p.Gln310Arg	missense_variant	11/19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTMR3	ENST00000401950.7 linkuse as main transcript	c.929A>G	p.Gln310Arg	missense_variant	11/20	1	NM_021090.4	P4	Q13615-1
	ENST00000624945.1 linkuse as main transcript	n.20285T>C		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes

AF:

0.000256

AC:

AN:

152112

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000725

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000514

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000255

AC:

AN:

251348

Hom.:

AF XY:

0.000258

AC XY:

AN XY:

135828

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.0000868

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.000185

Gnomad NFE exome

AF:

0.000449

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000335

AC:

489

AN:

1461442

Hom.:

Cov.:

AF XY:

0.000318

AC XY:

231

AN XY:

727038

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000928

Gnomad4 FIN exome

AF:

0.0000936

Gnomad4 NFE exome

AF:

0.000402

Gnomad4 OTH exome

AF:

0.000348

GnomAD4 genome

AF:

0.000256

AC:

AN:

152230

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000515

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000378

Hom.:

Bravo

AF:

0.000261

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000264

AC:

EpiCase

AF:

0.000491

EpiControl

AF:

0.000593

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

Jun 11, 2021

The c.929A>G (p.Q310R) alteration is located in exon 11 (coding exon 9) of the MTMR3 gene. This alteration results from a A to G substitution at nucleotide position 929, causing the glutamine (Q) at amino acid position 310 to be replaced by an arginine (R). 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

0.089

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.10

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.68

D;.;D;.;.

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.064

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.86

D;D;D;D;.

M_CAP

Benign

0.035

MetaRNN

Benign

0.10

T;T;T;T;T

MetaSVM

Benign

-0.33

MutationAssessor

Benign

0.93

L;L;.;L;L

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-1.8

N;N;N;N;N

REVEL

Uncertain

0.33

Sift

Benign

0.18

T;T;T;T;T

Sift4G

Benign

0.25

T;T;T;T;T

Polyphen

0.0040

B;B;.;B;B

Vest4

0.35

MVP

0.84

MPC

1.0

ClinPred

0.11

GERP RS

4.8

Varity_R

0.23

gMVP

0.67

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over