Genetic Variant NM_001142782.2:c.1229G>T (chr1-113622863-G-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001142782.2(MAGI3):c.1229G>T(p.Arg410Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000658 in 152,006 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R410Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MAGI3
NM_001142782.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.98

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGI3	NM_001142782.2 link	c.1229G>T	p.Arg410Leu	missense_variant	Exon 9 of 21	ENST00000307546.14	NP_001136254.1	Q5TCQ9-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MAGI3	ENST00000307546.14 link	c.1229G>T	p.Arg410Leu	missense_variant	Exon 9 of 21	5	NM_001142782.2	ENSP00000304604.9	Q5TCQ9-4
MAGI3	ENST00000369617.8 link	c.1304G>T	p.Arg435Leu	missense_variant	Exon 10 of 22	1		ENSP00000358630.4	Q5TCQ9-2
MAGI3	ENST00000369611.4 link	c.1229G>T	p.Arg410Leu	missense_variant	Exon 9 of 21	1		ENSP00000358624.4	Q5TCQ9-3
MAGI3	ENST00000369615.5 link	c.1229G>T	p.Arg410Leu	missense_variant	Exon 9 of 22	5		ENSP00000358628.1	Q5TCQ9-3

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152006

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1447986

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

719856

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152006

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74240

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.069

BayesDel_noAF

Benign

-0.34

CADD

Uncertain

DANN

Uncertain

0.99

Eigen

Uncertain

0.40

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.88

D;D;.;D

M_CAP

Benign

0.014

MetaRNN

Uncertain

0.68

D;D;D;D

MetaSVM

Benign

-0.95

MutationAssessor

Uncertain

2.0

M;.;.;.

PrimateAI

Uncertain

0.51

PROVEAN

Uncertain

-3.1

D;D;D;D

REVEL

Benign

0.11

Sift

Benign

0.23

T;T;T;T

Sift4G

Benign

0.086

T;T;T;T

Polyphen

0.56

P;.;P;P

Vest4

0.64

MutPred

0.57

.;Loss of MoRF binding (P = 0.002);Loss of MoRF binding (P = 0.002);Loss of MoRF binding (P = 0.002);

MVP

0.13

MPC

0.59

ClinPred

0.98

GERP RS

4.9

Varity_R

0.23

gMVP

0.54

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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