1-113646531-G-C
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_001142782.2(MAGI3):c.2044G>C(p.Glu682Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000484 in 1,612,448 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000048 ( 1 hom. )
Consequence
MAGI3
NM_001142782.2 missense
NM_001142782.2 missense
Scores
1
3
14
Clinical Significance
Conservation
PhyloP100: 8.46
Genes affected
MAGI3 (HGNC:29647): (membrane associated guanylate kinase, WW and PDZ domain containing 3) Predicted to enable frizzled binding activity. Predicted to be involved in signal transduction. Predicted to act upstream of or within positive regulation of JUN kinase activity. Located in cell junction. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.17521924).
BS2
?
High AC in GnomAd at 8 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MAGI3 | NM_001142782.2 | c.2044G>C | p.Glu682Gln | missense_variant | 12/21 | ENST00000307546.14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MAGI3 | ENST00000307546.14 | c.2044G>C | p.Glu682Gln | missense_variant | 12/21 | 5 | NM_001142782.2 | ||
MAGI3 | ENST00000369617.8 | c.2119G>C | p.Glu707Gln | missense_variant | 13/22 | 1 | |||
MAGI3 | ENST00000369611.4 | c.2044G>C | p.Glu682Gln | missense_variant | 12/21 | 1 | P1 | ||
MAGI3 | ENST00000369615.5 | c.2044G>C | p.Glu682Gln | missense_variant | 12/22 | 5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000526 AC: 8AN: 152134Hom.: 0 Cov.: 32
GnomAD3 genomes
?
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GnomAD3 exomes AF: 0.0000518 AC: 13AN: 250836Hom.: 0 AF XY: 0.0000516 AC XY: 7AN XY: 135580
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GnomAD4 exome AF: 0.0000479 AC: 70AN: 1460314Hom.: 1 Cov.: 30 AF XY: 0.0000496 AC XY: 36AN XY: 726396
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GnomAD4 genome ? AF: 0.0000526 AC: 8AN: 152134Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74318
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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 | Jul 06, 2021 | The c.2044G>C (p.E682Q) alteration is located in exon 12 (coding exon 12) of the MAGI3 gene. This alteration results from a G to C substitution at nucleotide position 2044, causing the glutamic acid (E) at amino acid position 682 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T;D;.;T
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;.;.
MutationTaster
Benign
D;D;D;D
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N;N
REVEL
Benign
Sift
Benign
T;T;T;T
Sift4G
Benign
T;T;T;T
Polyphen
B;.;P;P
Vest4
MVP
MPC
0.58
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
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Score
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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