5-32229924-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001040446.3(MTMR12):​c.2098G>A​(p.Ala700Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,240 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

MTMR12
NM_001040446.3 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.669
Variant links:
Genes affected
MTMR12 (HGNC:18191): (myotubularin related protein 12) Phosphatidylinositide 3-kinase-derived membrane-anchored phosphatidylinositides, such as phosphatidylinositol 3-phosphate (PtdIns(3)P), regulate diverse cellular processes. The protein encoded by this gene functions as an adaptor subunit in a complex with an active PtdIns(3)P 3-phosphatase. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2014]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.06279415).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MTMR12NM_001040446.3 linkc.2098G>A p.Ala700Thr missense_variant Exon 16 of 16 ENST00000382142.8 NP_001035536.1 Q9C0I1-1
MTMR12NM_001294343.2 linkc.1936G>A p.Ala646Thr missense_variant Exon 15 of 15 NP_001281272.1 Q9C0I1-2
MTMR12NM_001294344.2 linkc.1768G>A p.Ala590Thr missense_variant Exon 14 of 14 NP_001281273.1 Q9C0I1-3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MTMR12ENST00000382142.8 linkc.2098G>A p.Ala700Thr missense_variant Exon 16 of 16 1 NM_001040446.3 ENSP00000371577.3 Q9C0I1-1
MTMR12ENST00000280285.9 linkc.1936G>A p.Ala646Thr missense_variant Exon 15 of 15 1 ENSP00000280285.5 Q9C0I1-2
MTMR12ENST00000264934.5 linkc.1768G>A p.Ala590Thr missense_variant Exon 14 of 14 2 ENSP00000264934.5 Q9C0I1-3
MTMR12ENST00000510216.1 linkn.*161G>A downstream_gene_variant 2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000400
AC:
1
AN:
250130
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135134
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
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:
0.00000205
AC:
3
AN:
1460240
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
726264
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000756
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.00000824
AC:
1
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Apr 16, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.2098G>A (p.A700T) alteration is located in exon 16 (coding exon 16) of the MTMR12 gene. This alteration results from a G to A substitution at nucleotide position 2098, causing the alanine (A) at amino acid position 700 to be replaced by a threonine (T). 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
0.079
BayesDel_addAF
Benign
-0.14
T
BayesDel_noAF
Benign
-0.27
CADD
Benign
15
DANN
Uncertain
0.99
DEOGEN2
Benign
0.011
.;T;.
Eigen
Benign
-0.51
Eigen_PC
Benign
-0.35
FATHMM_MKL
Benign
0.52
D
LIST_S2
Benign
0.78
T;T;T
M_CAP
Benign
0.017
T
MetaRNN
Benign
0.063
T;T;T
MetaSVM
Uncertain
-0.23
T
MutationAssessor
Benign
0.20
.;N;.
PrimateAI
Benign
0.34
T
PROVEAN
Benign
-0.84
N;N;N
REVEL
Benign
0.26
Sift
Benign
0.35
T;T;T
Sift4G
Benign
0.28
T;T;T
Polyphen
0.0010
B;B;B
Vest4
0.048
MutPred
0.22
.;Gain of glycosylation at A700 (P = 0.0651);.;
MVP
0.38
MPC
0.46
ClinPred
0.19
T
GERP RS
4.4
Varity_R
0.056
gMVP
0.23

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: rs753474979; hg19: chr5-32230030; API