Variant 3-65357097-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001033057.2(MAGI1):c.3670C>T(p.Pro1224Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,190 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

MAGI1
NM_001033057.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.220

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03155926).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MAGI1	NM_001033057.2 linkuse as main transcript	c.3670C>T	p.Pro1224Ser	missense_variant	23/23	ENST00000402939.7	NP_001028229.1
MAGI1	NM_001365903.2 linkuse as main transcript	c.3849C>T	p.Val1283=	synonymous_variant	25/25		NP_001352832.1
MAGI1	NM_001365904.2 linkuse as main transcript	c.3846C>T	p.Val1282=	synonymous_variant	25/25		NP_001352833.1
MAGI1	NM_015520.2 linkuse as main transcript	c.3843C>T	p.Val1281=	synonymous_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.3670C>T	p.Pro1224Ser	missense_variant	23/23	1	NM_001033057.2	ENSP00000385450	A2	Q96QZ7-2
MAGI1	ENST00000621418.4 linkuse as main transcript	c.2749C>T	p.Pro917Ser	missense_variant	22/22	1		ENSP00000477591
MAGI1	ENST00000330909.12 linkuse as main transcript	c.3843C>T	p.Val1281=	synonymous_variant	25/25	1		ENSP00000331157	P4	Q96QZ7-5
MAGI1	ENST00000611645.4 linkuse as main transcript	c.2922C>T	p.Val974=	synonymous_variant	24/24	1		ENSP00000480920

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152190

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

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152190

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74340

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

Alfa

AF:

0.0000658

Hom.:

Bravo

AF:

0.0000113

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

Jul 09, 2021

The c.3670C>T (p.P1224S) 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 3670, causing the proline (P) at amino acid position 1224 to be replaced by a serine (S). 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

-0.37

BayesDel_noAF

Benign

-0.76

CADD

Benign

DANN

Benign

0.76

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.13

M_CAP

Benign

0.0034

MetaRNN

Benign

0.032

T;T

MetaSVM

Benign

-0.96

MutationTaster

Benign

1.0

D;N

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.070

.;N

REVEL

Benign

0.030

Sift

Benign

0.35

.;T

Sift4G

Benign

0.51

T;T

Polyphen

0.0040

.;B

Vest4

0.012

MVP

0.093

MPC

0.56

ClinPred

0.086

GERP RS

0.91

gMVP

0.14

Splicing

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over