Genetic Variant MAGI3:p.Gly1318Asp (chr1-113683521-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001142782.2(MAGI3):c.3953G>A(p.Gly1318Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0393 in 1,613,900 control chromosomes in the GnomAD database, including 1,570 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 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: 𝑓 0.029 ( 94 hom., cov: 32)

Exomes 𝑓: 0.040 ( 1476 hom. )

Consequence

MAGI3
NM_001142782.2 missense

Scores

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]

MAGI3 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_001142782.2, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0027545393).

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0919 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001142782.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAGI3	NM_001142782.2	MANE Select	c.3953G>A	p.Gly1318Asp	missense	Exon 21 of 21	NP_001136254.1	Q5TCQ9-4
	MAGI3	NM_152900.3		c.*1260G>A		3_prime_UTR	Exon 21 of 21	NP_690864.2	Q5TCQ9-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MAGI3	ENST00000307546.14	TSL:5 MANE Select	c.3953G>A	p.Gly1318Asp	missense	Exon 21 of 21	ENSP00000304604.9	Q5TCQ9-4
MAGI3	ENST00000955188.1		c.4046G>A	p.Gly1349Asp	missense	Exon 22 of 22	ENSP00000625247.1
MAGI3	ENST00000875357.1		c.4028G>A	p.Gly1343Asp	missense	Exon 22 of 22	ENSP00000545416.1

Frequencies

GnomAD3 genomes

AF:

0.0294

AC:

4472

AN:

152128

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00867

Gnomad AMI

AF:

0.0450

Gnomad AMR

AF:

0.0381

Gnomad ASJ

AF:

0.0225

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00746

Gnomad FIN

AF:

0.0188

Gnomad MID

AF:

0.108

Gnomad NFE

AF:

0.0450

Gnomad OTH

AF:

0.0411

GnomAD2 exomes

AF:

0.0286

AC:

7112

AN:

248544

AF XY:

0.0293

show subpopulations

Gnomad AFR exome

AF:

0.00741

Gnomad AMR exome

AF:

0.0263

Gnomad ASJ exome

AF:

0.0275

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0174

Gnomad NFE exome

AF:

0.0441

Gnomad OTH exome

AF:

0.0377

GnomAD4 exome

AF:

0.0404

AC:

59023

AN:

1461654

Hom.:

1476

Cov.:

AF XY:

0.0396

AC XY:

28802

AN XY:

727112

show subpopulations

African (AFR)

AF:

0.00839

AC:

281

AN:

33476

American (AMR)

AF:

0.0265

AC:

1185

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0274

AC:

717

AN:

26134

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39694

South Asian (SAS)

AF:

0.00925

AC:

798

AN:

86256

European-Finnish (FIN)

AF:

0.0183

AC:

975

AN:

53380

Middle Eastern (MID)

AF:

0.0986

AC:

569

AN:

5768

European-Non Finnish (NFE)

AF:

0.0469

AC:

52115

AN:

1111850

Other (OTH)

AF:

0.0395

AC:

2382

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

3270

6540

9809

13079

16349

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1940

3880

5820

7760

9700

<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

AF:

0.0294

AC:

4471

AN:

152246

Hom.:

Cov.:

AF XY:

0.0285

AC XY:

2125

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.00862

AC:

358

AN:

41544

American (AMR)

AF:

0.0380

AC:

581

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.0225

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00767

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0188

AC:

199

AN:

10608

Middle Eastern (MID)

AF:

0.112

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0450

AC:

3058

AN:

68012

Other (OTH)

AF:

0.0407

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

208

416

624

832

1040

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

150

200

250

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0374

Hom.:

267

Bravo

AF:

0.0296

Asia WGS

AF:

0.00722

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Benign

0.94

Eigen

Benign

-0.41

Eigen_PC

Benign

-0.57

FATHMM_MKL

Benign

0.037

LIST_S2

Benign

0.49

MetaRNN

Benign

0.0028

MetaSVM

Benign

-1.1

PhyloP100

0.23

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.69

REVEL

Benign

0.091

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.025

Varity_R

0.13

gMVP

0.28

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over