Variant 8-11300050-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_015458.4(MTMR9):c.319C>G(p.Leu107Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,202 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

MTMR9
NM_015458.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.20

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTMR9	NM_015458.4 link	c.319C>G	p.Leu107Val	missense_variant	3/10	ENST00000221086.8	NP_056273.2	Q96QG7-1
MTMR9	XM_047422125.1 link	c.319C>G	p.Leu107Val	missense_variant	3/11		XP_047278081.1
MTMR9	XM_017013753.3 link	c.319C>G	p.Leu107Val	missense_variant	3/7		XP_016869242.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTMR9	ENST00000221086.8 link	c.319C>G	p.Leu107Val	missense_variant	3/10	1	NM_015458.4	ENSP00000221086.3		Q96QG7-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461202

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726898

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00000360

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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

Oct 26, 2024

The c.319C>G (p.L107V) alteration is located in exon 3 (coding exon 3) of the MTMR9 gene. This alteration results from a C to G substitution at nucleotide position 319, causing the leucine (L) at amino acid position 107 to be replaced by a valine (V). 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

0.26

BayesDel_addAF

Pathogenic

0.26

BayesDel_noAF

Uncertain

0.13

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.13

T;.

Eigen

Benign

-0.038

Eigen_PC

Benign

0.12

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.89

D;D

M_CAP

Benign

0.034

MetaRNN

Uncertain

0.49

T;T

MetaSVM

Uncertain

0.26

MutationAssessor

Benign

1.6

L;.

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-1.4

N;N

REVEL

Uncertain

0.49

Sift

Benign

0.11

T;T

Sift4G

Benign

0.46

T;T

Polyphen

0.063

B;.

Vest4

0.58

MutPred

0.41

Loss of sheet (P = 0.1907);.;

MVP

0.94

MPC

0.0078

ClinPred

0.75

GERP RS

4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.074

gMVP

0.69

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over