Variant 8-11295251-G-T 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_015458.4(MTMR9):c.240G>T(p.Gln80His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000515 in 1,611,882 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: 31)

Exomes 𝑓: 0.000030 ( 0 hom. )

Consequence

MTMR9
NM_015458.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.95

Variant links:

Genes affected

MTMR9 (HGNC:14596): (myotubularin related protein 9) This gene encodes a myotubularin-related protein that is atypical to most other members of the myotubularin-related protein family because it has no dual-specificity phosphatase domain. The encoded protein contains a double-helical motif similar to the SET interaction domain, which is thought to have a role in the control of cell proliferation. In mouse, a protein similar to the encoded protein binds with MTMR7, and together they dephosphorylate phosphatidylinositol 3-phosphate and inositol 1,3-bisphosphate. [provided by RefSeq, Jul 2008]

MTMR9 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=0.08899224).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
MTMR9	NM_015458.4 linkuse as main transcript	c.240G>T	p.Gln80His	missense_variant	2/10	ENST00000221086.8
MTMR9	XM_047422125.1 linkuse as main transcript	c.240G>T	p.Gln80His	missense_variant	2/11
MTMR9	XM_017013753.3 linkuse as main transcript	c.240G>T	p.Gln80His	missense_variant	2/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTMR9	ENST00000221086.8 linkuse as main transcript	c.240G>T	p.Gln80His	missense_variant	2/10	1	NM_015458.4	P1	Q96QG7-1
MTMR9	ENST00000530200.1 linkuse as main transcript	c.240G>T	p.Gln80His	missense_variant, NMD_transcript_variant	2/11	1
MTMR9	ENST00000526292.1 linkuse as main transcript	c.-16G>T		5_prime_UTR_variant	2/10	2			Q96QG7-2
MTMR9	ENST00000528389.1 linkuse as main transcript	n.477G>T		non_coding_transcript_exon_variant	1/2	3

Frequencies

GnomAD3 genomes

AF:

0.000256

AC:

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000941

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000598

AC:

AN:

250768

Hom.:

AF XY:

0.0000443

AC XY:

AN XY:

135558

show subpopulations

Gnomad AFR exome

AF:

0.000924

Gnomad AMR exome

AF:

0.00

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:

0.00

GnomAD4 exome

AF:

0.0000301

AC:

AN:

1459696

Hom.:

Cov.:

AF XY:

0.0000248

AC XY:

AN XY:

726284

show subpopulations

Gnomad4 AFR exome

AF:

0.000928

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000630

Gnomad4 OTH exome

AF:

0.0000663

GnomAD4 genome

AF:

0.000256

AC:

AN:

152186

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.000941

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:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000248

Hom.:

Bravo

AF:

0.000306

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000906

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

May 13, 2024

The c.240G>T (p.Q80H) alteration is located in exon 2 (coding exon 2) of the MTMR9 gene. This alteration results from a G to T substitution at nucleotide position 240, causing the glutamine (Q) at amino acid position 80 to be replaced by a histidine (H). 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

0.22

BayesDel_addAF

Benign

-0.094

BayesDel_noAF

Uncertain

0.040

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.11

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.052

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.025

MetaRNN

Benign

0.089

MetaSVM

Benign

-0.56

MutationAssessor

Benign

1.3

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-1.9

REVEL

Uncertain

0.41

Sift

Benign

0.17

Sift4G

Benign

0.23

Polyphen

0.026

Vest4

0.56

MutPred

0.47

Loss of sheet (P = 0.0817);

MVP

0.76

MPC

0.0071

ClinPred

0.074

GERP RS

3.5

Varity_R

0.16

gMVP

0.84

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