rs145260557

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001040446.3(MTMR12):​c.1667G>T​(p.Arg556Leu) 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 1,461,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R556C) has been classified as Uncertain significance.

Frequency

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

Consequence

MTMR12
NM_001040446.3 missense

Scores

9
10

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.564
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.35707527).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MTMR12NM_001040446.3 linkc.1667G>T p.Arg556Leu missense_variant Exon 15 of 16 ENST00000382142.8 NP_001035536.1 Q9C0I1-1
MTMR12NM_001294343.2 linkc.1512+1182G>T intron_variant Intron 14 of 14 NP_001281272.1 Q9C0I1-2
MTMR12NM_001294344.2 linkc.1345-3433G>T intron_variant Intron 13 of 13 NP_001281273.1 Q9C0I1-3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MTMR12ENST00000382142.8 linkc.1667G>T p.Arg556Leu missense_variant Exon 15 of 16 1 NM_001040446.3 ENSP00000371577.3 Q9C0I1-1
MTMR12ENST00000280285.9 linkc.1512+1182G>T intron_variant Intron 14 of 14 1 ENSP00000280285.5 Q9C0I1-2
MTMR12ENST00000264934.5 linkc.1345-3433G>T intron_variant Intron 13 of 13 2 ENSP00000264934.5 Q9C0I1-3
MTMR12ENST00000510216.1 linkn.114G>T non_coding_transcript_exon_variant Exon 1 of 3 2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251474
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135908
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000289
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:
0.00000205
AC:
3
AN:
1461890
Hom.:
0
Cov.:
31
AF XY:
0.00000413
AC XY:
3
AN XY:
727244
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.14
BayesDel_addAF
Uncertain
0.065
T
BayesDel_noAF
Uncertain
-0.060
CADD
Benign
18
DANN
Uncertain
0.99
DEOGEN2
Benign
0.018
T
Eigen
Benign
-0.74
Eigen_PC
Benign
-0.79
FATHMM_MKL
Benign
0.47
N
LIST_S2
Uncertain
0.91
D
M_CAP
Uncertain
0.17
D
MetaRNN
Benign
0.36
T
MetaSVM
Uncertain
-0.28
T
MutationAssessor
Benign
2.0
M
PrimateAI
Benign
0.21
T
PROVEAN
Benign
-1.8
N
REVEL
Uncertain
0.33
Sift
Uncertain
0.018
D
Sift4G
Uncertain
0.037
D
Polyphen
0.36
B
Vest4
0.65
MutPred
0.35
Loss of solvent accessibility (P = 0.0238);
MVP
0.37
MPC
0.76
ClinPred
0.12
T
GERP RS
-1.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.14
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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs145260557; hg19: chr5-32233886; API