chr22-30019706-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_021090.4(MTMR3):c.2047G>A(p.Gly683Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000322 in 1,614,104 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000033 ( 0 hom. )
Consequence
MTMR3
NM_021090.4 missense
NM_021090.4 missense
Scores
6
7
6
Clinical Significance
Conservation
PhyloP100: 7.58
Genes affected
MTMR3 (HGNC:7451): (myotubularin related protein 3) This gene encodes a member of the myotubularin dual specificity protein phosphatase gene family. The encoded protein is structurally similar to myotubularin but in addition contains a FYVE domain and an N-terminal PH-GRAM domain. The protein can self-associate and also form heteromers with another myotubularin related protein. The protein binds to phosphoinositide lipids through the PH-GRAM domain, and can hydrolyze phosphatidylinositol(3)-phosphate and phosphatidylinositol(3,5)-biphosphate in vitro. The encoded protein has been observed to have a perinuclear, possibly membrane-bound, distribution in cells, but it has also been found free in the cytoplasm. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MTMR3 | NM_021090.4 | c.2047G>A | p.Gly683Arg | missense_variant | 17/20 | ENST00000401950.7 | |
HORMAD2-AS1 | NR_110541.2 | n.362-977C>T | intron_variant, non_coding_transcript_variant | ||||
MTMR3 | NM_153050.3 | c.2047G>A | p.Gly683Arg | missense_variant | 17/20 | ||
MTMR3 | NM_153051.3 | c.2047G>A | p.Gly683Arg | missense_variant | 17/19 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MTMR3 | ENST00000401950.7 | c.2047G>A | p.Gly683Arg | missense_variant | 17/20 | 1 | NM_021090.4 | P4 | |
ENST00000624945.1 | n.8531C>T | non_coding_transcript_exon_variant | 1/1 | ||||||
HORMAD2-AS1 | ENST00000429350.5 | n.335-977C>T | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152222Hom.: 0 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000677 AC: 17AN: 251258Hom.: 0 AF XY: 0.0000883 AC XY: 12AN XY: 135846
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GnomAD4 exome AF: 0.0000328 AC: 48AN: 1461882Hom.: 0 Cov.: 30 AF XY: 0.0000385 AC XY: 28AN XY: 727242
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GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152222Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74368
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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 | May 27, 2022 | The c.2047G>A (p.G683R) alteration is located in exon 17 (coding exon 15) of the MTMR3 gene. This alteration results from a G to A substitution at nucleotide position 2047, causing the glycine (G) at amino acid position 683 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Pathogenic
DEOGEN2
Benign
T;.;T;.;.
Eigen
Uncertain
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D;D;D;.
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Benign
L;L;.;L;L
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N;N
REVEL
Uncertain
Sift
Uncertain
D;D;D;D;D
Sift4G
Benign
T;T;T;T;T
Polyphen
D;D;.;D;D
Vest4
MutPred
Gain of solvent accessibility (P = 0.0097);Gain of solvent accessibility (P = 0.0097);.;Gain of solvent accessibility (P = 0.0097);Gain of solvent accessibility (P = 0.0097);
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at