chr3-65379477-C-T

Variant summary

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

The NM_001033057.2(MAGI1):​c.2779G>A​(p.Glu927Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. E927Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

MAGI1
NM_001033057.2 missense

Scores

1
4
12

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.65
Variant links:
Genes affected
MAGI1 (HGNC:946): (membrane associated guanylate kinase, WW and PDZ domain containing 1) The protein encoded by this gene is a member of the membrane-associated guanylate kinase homologue (MAGUK) family. MAGUK proteins participate in the assembly of multiprotein complexes on the inner surface of the plasma membrane at regions of cell-cell contact. The product of this gene may play a role as scaffolding protein at cell-cell junctions. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

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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=0.3201071).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MAGI1NM_001033057.2 linkc.2779G>A p.Glu927Lys missense_variant Exon 17 of 23 ENST00000402939.7 NP_001028229.1 Q96QZ7-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MAGI1ENST00000402939.7 linkc.2779G>A p.Glu927Lys missense_variant Exon 17 of 23 1 NM_001033057.2 ENSP00000385450.2 Q96QZ7-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.082
T
BayesDel_noAF
Benign
-0.36
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.10
.;.;T;.;.;.;.;.
Eigen
Uncertain
0.30
Eigen_PC
Uncertain
0.38
FATHMM_MKL
Pathogenic
0.99
D
M_CAP
Benign
0.026
D
MetaRNN
Benign
0.32
T;T;T;T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.7
L;.;.;.;.;L;.;.
PrimateAI
Uncertain
0.74
T
PROVEAN
Benign
-1.9
N;.;.;N;N;N;N;N
REVEL
Benign
0.095
Sift
Benign
0.33
T;.;.;T;T;T;T;T
Sift4G
Benign
0.28
T;T;T;T;T;T;T;T
Polyphen
0.71
P;.;.;P;.;D;P;.
Vest4
0.58
MutPred
0.38
Gain of ubiquitination at E955 (P = 0.0054);.;.;.;.;Gain of ubiquitination at E955 (P = 0.0054);.;.;
MVP
0.48
MPC
1.2
ClinPred
0.93
D
GERP RS
5.5
gMVP
0.45

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs745320055; hg19: chr3-65365152; API