3-65361240-C-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_001033057.2(MAGI1):​c.3593G>A​(p.Arg1198His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000204 in 1,614,164 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

MAGI1
NM_001033057.2 missense

Scores

5
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.73
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.35748506).
BS2
High AC in GnomAd4 at 5 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MAGI1NM_001033057.2 linkc.3593G>A p.Arg1198His missense_variant Exon 22 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.3593G>A p.Arg1198His missense_variant Exon 22 of 23 1 NM_001033057.2 ENSP00000385450.2 Q96QZ7-2

Frequencies

GnomAD3 genomes
AF:
0.0000329
AC:
5
AN:
152202
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251390
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135884
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000192
AC:
28
AN:
1461844
Hom.:
0
Cov.:
33
AF XY:
0.0000138
AC XY:
10
AN XY:
727226
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000243
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000328
AC:
5
AN:
152320
Hom.:
0
Cov.:
32
AF XY:
0.0000537
AC XY:
4
AN XY:
74494
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000113
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Dec 22, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.3593G>A (p.R1198H) alteration is located in exon 22 (coding exon 22) of the MAGI1 gene. This alteration results from a G to A substitution at nucleotide position 3593, causing the arginine (R) at amino acid position 1198 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.18
T
BayesDel_noAF
Benign
-0.40
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Benign
0.099
.;.;T;.;.;.;.;.
Eigen
Uncertain
0.41
Eigen_PC
Uncertain
0.47
FATHMM_MKL
Uncertain
0.90
D
M_CAP
Benign
0.020
T
MetaRNN
Benign
0.36
T;T;T;T;T;T;T;T
MetaSVM
Benign
-0.34
T
MutationAssessor
Benign
0.96
.;.;.;.;.;L;.;.
PrimateAI
Uncertain
0.71
T
PROVEAN
Benign
-2.3
N;.;.;N;N;N;N;N
REVEL
Benign
0.13
Sift
Benign
0.10
T;.;.;T;T;T;T;T
Sift4G
Benign
0.18
T;T;T;T;T;T;T;T
Polyphen
0.019
B;.;.;B;.;B;D;.
Vest4
0.45
MutPred
0.58
Loss of MoRF binding (P = 0.0443);.;.;.;.;.;.;.;
MVP
0.11
MPC
0.75
ClinPred
0.65
D
GERP RS
5.6
gMVP
0.38

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
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: rs1339656333; hg19: chr3-65346915; COSMIC: COSV58322089; COSMIC: COSV58322089; API