1-149931420-C-G

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

3
16

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]

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=0.22473484).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MTMR11NM_001145862.2 linkc.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
MTMR11ENST00000439741.4 linkc.1130G>C p.Gly377Ala missense_variant Exon 13 of 17 2 NM_001145862.2 ENSP00000391668.2 A4FU01-1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD3 exomes
AF:
0.0000212
AC:
5
AN:
235862
Hom.:
0
AF XY:
0.00000785
AC XY:
1
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:
7
AN:
1446002
Hom.:
0
Cov.:
31
AF XY:
0.00000278
AC XY:
2
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.:
31
Bravo
AF:
0.00000756
ExAC
AF:
0.00000824
AC:
1

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
T
BayesDel_noAF
Benign
-0.20
CADD
Benign
21
DANN
Uncertain
0.98
DEOGEN2
Benign
0.20
.;T
Eigen
Benign
-0.058
Eigen_PC
Benign
0.17
FATHMM_MKL
Benign
0.73
D
LIST_S2
Uncertain
0.86
D;D
M_CAP
Benign
0.014
T
MetaRNN
Benign
0.22
T;T
MetaSVM
Benign
-0.42
T
MutationAssessor
Benign
0.17
.;N
PrimateAI
Benign
0.41
T
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
T
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.

Other links and lift over

dbSNP: rs782070877; hg19: chr1-149903312; API