1-113643746-C-T
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_001142782.2(MAGI3):c.1970C>T(p.Pro657Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000366 in 1,613,448 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: 𝑓 0.000039 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000036 ( 0 hom. )
Consequence
MAGI3
NM_001142782.2 missense
NM_001142782.2 missense
Scores
1
2
15
Clinical Significance
Conservation
PhyloP100: 5.09
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=0.13674295).
BS2
?
High AC in GnomAd at 6 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MAGI3 | NM_001142782.2 | c.1970C>T | p.Pro657Leu | missense_variant | 11/21 | ENST00000307546.14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MAGI3 | ENST00000307546.14 | c.1970C>T | p.Pro657Leu | missense_variant | 11/21 | 5 | NM_001142782.2 | ||
MAGI3 | ENST00000369617.8 | c.2045C>T | p.Pro682Leu | missense_variant | 12/22 | 1 | |||
MAGI3 | ENST00000369611.4 | c.1970C>T | p.Pro657Leu | missense_variant | 11/21 | 1 | P1 | ||
MAGI3 | ENST00000369615.5 | c.1970C>T | p.Pro657Leu | missense_variant | 11/22 | 5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000395 AC: 6AN: 151796Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000557 AC: 14AN: 251288Hom.: 0 AF XY: 0.0000810 AC XY: 11AN XY: 135818
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GnomAD4 exome AF: 0.0000363 AC: 53AN: 1461534Hom.: 0 Cov.: 31 AF XY: 0.0000399 AC XY: 29AN XY: 727080
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GnomAD4 genome ? AF: 0.0000395 AC: 6AN: 151914Hom.: 0 Cov.: 32 AF XY: 0.0000674 AC XY: 5AN XY: 74234
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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 | Sep 25, 2023 | The c.1970C>T (p.P657L) alteration is located in exon 11 (coding exon 11) of the MAGI3 gene. This alteration results from a C to T substitution at nucleotide position 1970, causing the proline (P) at amino acid position 657 to be replaced by a leucine (L). 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
Benign
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;T;.;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;.;.
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;.;P;P
Vest4
MutPred
0.41
.;Loss of glycosylation at P657 (P = 0.0079);Loss of glycosylation at P657 (P = 0.0079);Loss of glycosylation at P657 (P = 0.0079);
MVP
MPC
0.30
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