chr1-113642462-G-A
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_001142782.2(MAGI3):c.1912G>A(p.Val638Met) variant causes a missense change. The variant allele was found at a frequency of 0.00000821 in 1,461,780 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000082 ( 0 hom. )
Consequence
MAGI3
NM_001142782.2 missense
NM_001142782.2 missense
Scores
4
14
Clinical Significance
Conservation
PhyloP100: 4.28
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=0.09511113).
BS2
?
High AC in GnomAdExome at 5 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MAGI3 | NM_001142782.2 | c.1912G>A | p.Val638Met | missense_variant | 10/21 | ENST00000307546.14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MAGI3 | ENST00000307546.14 | c.1912G>A | p.Val638Met | missense_variant | 10/21 | 5 | NM_001142782.2 | ||
MAGI3 | ENST00000369617.8 | c.1987G>A | p.Val663Met | missense_variant | 11/22 | 1 | |||
MAGI3 | ENST00000369611.4 | c.1912G>A | p.Val638Met | missense_variant | 10/21 | 1 | P1 | ||
MAGI3 | ENST00000369615.5 | c.1912G>A | p.Val638Met | missense_variant | 10/22 | 5 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 genomes
?
Cov.:
31
GnomAD3 exomes AF: 0.0000201 AC: 5AN: 248994Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 134798
GnomAD3 exomes
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GnomAD4 exome AF: 0.00000821 AC: 12AN: 1461780Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5AN XY: 727178
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GnomAD4 genome ? Cov.: 31
GnomAD4 genome
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Cov.:
31
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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 | Aug 08, 2022 | The c.1912G>A (p.V638M) alteration is located in exon 10 (coding exon 10) of the MAGI3 gene. This alteration results from a G to A substitution at nucleotide position 1912, causing the valine (V) at amino acid position 638 to be replaced by a methionine (M). 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
Benign
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;.;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;.;.;.
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N
REVEL
Benign
Sift
Benign
T;T;T;T
Sift4G
Benign
T;T;T;T
Polyphen
B;.;D;D
Vest4
MutPred
0.33
.;Loss of helix (P = 0.0626);Loss of helix (P = 0.0626);Loss of helix (P = 0.0626);
MVP
MPC
0.67
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at