Variant 3-65356662-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001033057.2(MAGI1):c.4105C>T(p.Arg1369Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 10/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MAGI1
NM_001033057.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.26

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]

MAGI1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2321204).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MAGI1	NM_001033057.2 linkuse as main transcript	c.4105C>T	p.Arg1369Trp	missense_variant	23/23	ENST00000402939.7	NP_001028229.1
MAGI1	NM_001365903.2 linkuse as main transcript	c.*414C>T		3_prime_UTR_variant	25/25		NP_001352832.1
MAGI1	NM_001365904.2 linkuse as main transcript	c.*414C>T		3_prime_UTR_variant	25/25		NP_001352833.1
MAGI1	NM_015520.2 linkuse as main transcript	c.*414C>T		3_prime_UTR_variant	25/25		NP_056335.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAGI1	ENST00000402939.7 linkuse as main transcript	c.4105C>T	p.Arg1369Trp	missense_variant	23/23	1	NM_001033057.2	ENSP00000385450	A2	Q96QZ7-2
MAGI1	ENST00000621418.4 linkuse as main transcript	c.3184C>T	p.Arg1062Trp	missense_variant	22/22	1		ENSP00000477591
MAGI1	ENST00000330909.12 linkuse as main transcript	c.*414C>T		3_prime_UTR_variant	25/25	1		ENSP00000331157	P4	Q96QZ7-5
MAGI1	ENST00000611645.4 linkuse as main transcript	c.*414C>T		3_prime_UTR_variant	24/24	1		ENSP00000480920

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1431478

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

709914

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

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 26, 2021

The c.4105C>T (p.R1369W) alteration is located in exon 23 (coding exon 23) of the MAGI1 gene. This alteration results from a C to T substitution at nucleotide position 4105, causing the arginine (R) at amino acid position 1369 to be replaced by a tryptophan (W). 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

-0.16

BayesDel_noAF

Benign

-0.47

CADD

Uncertain

DANN

Uncertain

1.0

Eigen

Benign

0.026

Eigen_PC

Benign

-0.0046

FATHMM_MKL

Uncertain

0.81

M_CAP

Benign

0.017

MetaRNN

Benign

0.23

T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

0.58

D;D

PrimateAI

Benign

0.46

PROVEAN

Benign

-1.9

.;N

REVEL

Benign

0.061

Sift

Uncertain

0.0010

.;D

Sift4G

Uncertain

0.0020

D;D

Polyphen

0.99

.;D

Vest4

0.33

MutPred

0.33

.;Loss of helix (P = 0.1706);

MVP

0.24

MPC

0.58

ClinPred

0.89

GERP RS

3.3

gMVP

0.49

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over