Variant rs61742849 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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. 14/19 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

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

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MAGI3	NM_001142782.2 linkuse as main transcript	c.3953G>A	p.Gly1318Asp	missense_variant	21/21	ENST00000307546.14	NP_001136254.1
MAGI3	NM_152900.3 linkuse as main transcript	c.*1260G>A		3_prime_UTR_variant	21/21		NP_690864.2
MAGI3	XM_005270737.4 linkuse as main transcript	c.*666G>A		3_prime_UTR_variant	22/22		XP_005270794.1
MAGI3	XM_017000974.2 linkuse as main transcript	c.*634G>A		3_prime_UTR_variant	22/22		XP_016856463.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAGI3	ENST00000307546.14 linkuse as main transcript	c.3953G>A	p.Gly1318Asp	missense_variant	21/21	5	NM_001142782.2	ENSP00000304604		Q5TCQ9-4
MAGI3	ENST00000369615.5 linkuse as main transcript	c.*666G>A		3_prime_UTR_variant	22/22	5		ENSP00000358628	P1	Q5TCQ9-3

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

GnomAD3 exomes

AF:

0.0286

AC:

7112

AN:

248544

Hom.:

144

AF XY:

0.0293

AC XY:

3957

AN XY:

135108

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 SAS exome

AF:

0.00837

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

Gnomad4 AFR exome

AF:

0.00839

Gnomad4 AMR exome

AF:

0.0265

Gnomad4 ASJ exome

AF:

0.0274

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00925

Gnomad4 FIN exome

AF:

0.0183

Gnomad4 NFE exome

AF:

0.0469

Gnomad4 OTH exome

AF:

0.0395

GnomAD4 genome

AF:

0.0294

AC:

4471

AN:

152246

Hom.:

Cov.:

AF XY:

0.0285

AC XY:

2125

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.00862

Gnomad4 AMR

AF:

0.0380

Gnomad4 ASJ

AF:

0.0225

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00767

Gnomad4 FIN

AF:

0.0188

Gnomad4 NFE

AF:

0.0450

Gnomad4 OTH

AF:

0.0407

Alfa

AF:

0.0399

Hom.:

205

Bravo

AF:

0.0296

TwinsUK

AF:

0.0434

AC:

161

ALSPAC

AF:

0.0431

AC:

166

ESP6500AA

AF:

0.00957

AC:

ESP6500EA

AF:

0.0470

AC:

337

ExAC

AF:

0.0272

AC:

3277

Asia WGS

AF:

0.00722

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.44

CADD

Benign

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

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.69

REVEL

Benign

0.091

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.025

Vest4

0.11

MPC

0.37

ClinPred

0.035

GERP RS

2.2

Varity_R

0.13

gMVP

0.28

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over