3-65589685-A-C

Variant names:

• chr3-65589685-A-C
• rs12635482
• NM_001033057.2:c.430+32287T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001033057.2(MAGI1):​c.430+32287T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.371 in 151,732 control chromosomes in the GnomAD database, including 11,841 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.37 (11841 hom., cov: 30)
• Consequence: MAGI1 NM_001033057.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.30
• Publications: 3 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.642 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGI1	NM_001033057.2	c.430+32287T>G		intron_variant	Intron 2 of 22	ENST00000402939.7	NP_001028229.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAGI1	ENST00000402939.7	c.430+32287T>G		intron_variant	Intron 2 of 22	1	NM_001033057.2	ENSP00000385450.2

Frequencies

GnomAD3 genomes AF: 0.371 AC: 56286 AN: 151612 Hom.: 11837 Cov.: 30

Gnomad AFR AF: 0.176

Gnomad AMI AF: 0.363

Gnomad AMR AF: 0.391

Gnomad ASJ AF: 0.378

Gnomad EAS AF: 0.661

Gnomad SAS AF: 0.420

Gnomad FIN AF: 0.540

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.435

Gnomad OTH AF: 0.347

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.371 AC: 56316 AN: 151732 Hom.: 11841 Cov.: 30 AF XY: 0.378 AC XY: 28012 AN XY: 74128

African (AFR) AF: 0.176 AC: 7294 AN: 41390

American (AMR) AF: 0.392 AC: 5976 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.378 AC: 1311 AN: 3468

East Asian (EAS) AF: 0.661 AC: 3387 AN: 5124

South Asian (SAS) AF: 0.418 AC: 2005 AN: 4794

European-Finnish (FIN) AF: 0.540 AC: 5677 AN: 10520

Middle Eastern (MID) AF: 0.318 AC: 93 AN: 292

European-Non Finnish (NFE) AF: 0.435 AC: 29513 AN: 67866

Other (OTH) AF: 0.347 AC: 730 AN: 2106

Alfa AF: 0.296 Hom.: 985

Bravo AF: 0.352

Asia WGS AF: 0.483 AC: 1678 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.0040
DANN	Benign	0.60
PhyloP100		-3.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12635482; hg19: chr3-65575360;