Genetic Variant MTMR11:p.Gly377Ala (chr1-149931420-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_001145862.2(MTMR11):c.1130G>C(p.Gly377Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000484 in 1,446,002 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G377S) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

MTMR11
NM_001145862.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.13

Variant links:

Genes affected

MTMR11 (HGNC:24307): (myotubularin related protein 11) Predicted to enable phosphatidylinositol-3-phosphatase activity. Predicted to be involved in phosphatidylinositol dephosphorylation. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

MTMR11 links:

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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=0.22473484).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTMR11	NM_001145862.2 link	c.1130G>C	p.Gly377Ala	missense_variant	Exon 13 of 17	ENST00000439741.4	NP_001139334.1	A4FU01-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTMR11	ENST00000439741.4 link	c.1130G>C	p.Gly377Ala	missense_variant	Exon 13 of 17	2	NM_001145862.2	ENSP00000391668.2		A4FU01-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000212

AC:

AN:

235862

Hom.:

AF XY:

0.00000785

AC XY:

AN XY:

127414

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000156

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:

0.00000484

AC:

AN:

1446002

Hom.:

Cov.:

AF XY:

0.00000278

AC XY:

AN XY:

718302

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000142

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:

0.00

Gnomad4 OTH exome

AF:

0.0000168

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 13, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1130G>C (p.G377A) alteration is located in exon 13 (coding exon 13) of the MTMR11 gene. This alteration results from a G to C substitution at nucleotide position 1130, causing the glycine (G) at amino acid position 377 to be replaced by an alanine (A). 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

0.10

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.20

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.20

.;T

Eigen

Benign

-0.058

Eigen_PC

Benign

0.17

FATHMM_MKL

Benign

0.73

LIST_S2

Uncertain

0.86

D;D

M_CAP

Benign

0.014

MetaRNN

Benign

0.22

T;T

MetaSVM

Benign

-0.42

MutationAssessor

Benign

0.17

.;N

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.22

N;N

REVEL

Uncertain

0.31

Sift

Benign

0.19

T;T

Sift4G

Benign

0.72

T;T

Polyphen

0.021

B;B

Vest4

0.33

MutPred

0.49

.;Loss of disorder (P = 0.1004);

MVP

0.77

MPC

0.23

ClinPred

0.081

GERP RS

6.0

Varity_R

0.070

gMVP

0.28

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