dbSNP rs149468264: MAGI1:p.Val971Leu (chr3-65379345-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001033057.2(MAGI1):c.2911G>T(p.Val971Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,238 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. V971M) has been classified as Uncertain significance.

Frequency

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

Consequence

MAGI1
NM_001033057.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.78

Publications

1 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001033057.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MAGI1	NM_001033057.2	MANE Select	c.2911G>T	p.Val971Leu	missense	Exon 17 of 23	NP_001028229.1	Q96QZ7-2
MAGI1	NM_001365903.2		c.2998G>T	p.Val1000Leu	missense	Exon 18 of 25	NP_001352832.1
MAGI1	NM_001365904.2		c.2998G>T	p.Val1000Leu	missense	Exon 18 of 25	NP_001352833.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MAGI1	ENST00000402939.7	TSL:1 MANE Select	c.2911G>T	p.Val971Leu	missense	Exon 17 of 23	ENSP00000385450.2	Q96QZ7-2
MAGI1	ENST00000330909.12	TSL:1	c.2995G>T	p.Val999Leu	missense	Exon 18 of 25	ENSP00000331157.7	Q96QZ7-5
MAGI1	ENST00000483466.5	TSL:1	c.2995G>T	p.Val999Leu	missense	Exon 18 of 23	ENSP00000420323.1	Q96QZ7-3

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152238

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74378

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41468

American (AMR)

AF:

0.0000654

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68052

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.96

BayesDel_addAF

Pathogenic

0.20

BayesDel_noAF

Uncertain

0.060

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.26

Eigen

Benign

0.083

Eigen_PC

Benign

0.17

FATHMM_MKL

Pathogenic

1.0

M_CAP

Benign

0.037

MetaRNN

Uncertain

0.70

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

PhyloP100

7.8

PrimateAI

Uncertain

0.68

PROVEAN

Uncertain

-2.8

REVEL

Benign

0.26

Sift

Uncertain

0.016

Sift4G

Uncertain

0.017

Polyphen

0.12

Vest4

0.92

MutPred

0.56

Loss of disorder (P = 0.1132)

MVP

0.52

MPC

1.4

ClinPred

0.98

GERP RS

4.6

gMVP

0.71

Mutation Taster

=43/57

disease causing

(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

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over