Variant 8-11306311-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_015458.4(MTMR9):c.713C>G(p.Ser238Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,760 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

MTMR9
NM_015458.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.03

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 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.835

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MTMR9	NM_015458.4 linkuse as main transcript	c.713C>G	p.Ser238Cys	missense_variant	5/10	ENST00000221086.8	NP_056273.2
MTMR9	XM_047422125.1 linkuse as main transcript	c.713C>G	p.Ser238Cys	missense_variant	5/11		XP_047278081.1
MTMR9	XM_011543831.3 linkuse as main transcript	c.125C>G	p.Ser42Cys	missense_variant	3/8		XP_011542133.1
MTMR9	XM_017013753.3 linkuse as main transcript	c.713C>G	p.Ser238Cys	missense_variant	5/7		XP_016869242.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTMR9	ENST00000221086.8 linkuse as main transcript	c.713C>G	p.Ser238Cys	missense_variant	5/10	1	NM_015458.4	ENSP00000221086	P1	Q96QG7-1
MTMR9	ENST00000530200.1 linkuse as main transcript	c.*459C>G		3_prime_UTR_variant, NMD_transcript_variant	6/11	1		ENSP00000436046
MTMR9	ENST00000526292.1 linkuse as main transcript	c.458C>G	p.Ser153Cys	missense_variant	5/10	2		ENSP00000433239		Q96QG7-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461760

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727174

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Mar 14, 2023

The c.713C>G (p.S238C) alteration is located in exon 5 (coding exon 5) of the MTMR9 gene. This alteration results from a C to G substitution at nucleotide position 713, causing the serine (S) at amino acid position 238 to be replaced by a cysteine (C). 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

0.11

BayesDel_addAF

Uncertain

0.093

BayesDel_noAF

Benign

-0.10

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Pathogenic

0.89

D;.

Eigen

Uncertain

0.44

Eigen_PC

Uncertain

0.32

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.94

D;D

M_CAP

Uncertain

0.16

MetaRNN

Pathogenic

0.83

D;D

MetaSVM

Pathogenic

1.0

MutationAssessor

Uncertain

2.6

M;.

MutationTaster

Benign

0.89

D;D

PrimateAI

Benign

0.47

PROVEAN

Uncertain

-3.8

D;D

REVEL

Uncertain

0.46

Sift

Uncertain

0.0050

D;D

Sift4G

Uncertain

0.016

D;D

Polyphen

0.98

D;.

Vest4

0.39

MutPred

0.80

Loss of disorder (P = 0.0499);.;

MVP

0.95

MPC

0.035

ClinPred

0.94

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.22

gMVP

0.48

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