chr1-113683521-G-C

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001142782.2(MAGI3):​c.3953G>C​(p.Gly1318Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000151 in 1,461,674 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

MAGI3
NM_001142782.2 missense

Scores

1
1
15

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.225

Publications

21 publications found
Variant links:
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 was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.06704289).
BS2
High AC in GnomAdExome4 at 22 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MAGI3NM_001142782.2 linkc.3953G>C p.Gly1318Ala missense_variant Exon 21 of 21 ENST00000307546.14 NP_001136254.1 Q5TCQ9-4
MAGI3NM_152900.3 linkc.*1260G>C 3_prime_UTR_variant Exon 21 of 21 NP_690864.2 Q5TCQ9-3
MAGI3XM_017000974.2 linkc.*634G>C 3_prime_UTR_variant Exon 22 of 22 XP_016856463.1
MAGI3XM_005270737.4 linkc.*666G>C 3_prime_UTR_variant Exon 22 of 22 XP_005270794.1 Q5TCQ9-3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MAGI3ENST00000307546.14 linkc.3953G>C p.Gly1318Ala missense_variant Exon 21 of 21 5 NM_001142782.2 ENSP00000304604.9 Q5TCQ9-4
MAGI3ENST00000369615.5 linkc.*666G>C 3_prime_UTR_variant Exon 22 of 22 5 ENSP00000358628.1 Q5TCQ9-3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD2 exomes
AF:
0.0000161
AC:
4
AN:
248544
AF XY:
0.0000148
show subpopulations
Gnomad AFR exome
AF:
0.0000650
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000267
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000151
AC:
22
AN:
1461674
Hom.:
0
Cov.:
34
AF XY:
0.0000165
AC XY:
12
AN XY:
727116
show subpopulations
African (AFR)
AF:
0.0000299
AC:
1
AN:
33478
American (AMR)
AF:
0.0000224
AC:
1
AN:
44722
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26136
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39694
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86256
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53380
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
0.0000171
AC:
19
AN:
1111866
Other (OTH)
AF:
0.0000166
AC:
1
AN:
60374
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.470
Heterozygous variant carriers
0
2
4
6
8
10
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.00
Hom.:
267
ExAC
AF:
0.0000166
AC:
2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.074
BayesDel_addAF
Benign
-0.38
T
BayesDel_noAF
Benign
-0.61
CADD
Benign
9.4
DANN
Benign
0.88
Eigen
Benign
-0.87
Eigen_PC
Benign
-0.89
FATHMM_MKL
Benign
0.11
N
LIST_S2
Benign
0.55
T
M_CAP
Benign
0.014
T
MetaRNN
Benign
0.067
T
MetaSVM
Benign
-1.0
T
PhyloP100
0.23
PrimateAI
Benign
0.29
T
PROVEAN
Benign
-0.74
N
REVEL
Benign
0.023
Sift
Pathogenic
0.0
D
Sift4G
Uncertain
0.041
D
Vest4
0.071
MutPred
0.13
Loss of catalytic residue at A1317 (P = 0.0631);
MVP
0.13
MPC
0.17
ClinPred
0.12
T
GERP RS
2.2
Varity_R
0.10
gMVP
0.22
Mutation Taster
=94/6
polymorphism

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

Other links and lift over

dbSNP: rs61742849; hg19: chr1-114226143; API