3-65594823-G-T

Position:

• chr3-65594823-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001033057.2(MAGI1):​c.430+27149C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.352 in 151,968 control chromosomes in the GnomAD database, including 10,591 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 0.35 (10591 hom., cov: 32)
• Consequence: MAGI1 NM_001033057.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.647

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.571 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAGI1	NM_001033057.2	c.430+27149C>A		intron_variant		ENST00000402939.7	NP_001028229.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAGI1	ENST00000402939.7	c.430+27149C>A		intron_variant		1	NM_001033057.2	ENSP00000385450	A2

Frequencies

GnomAD3 genomes AF: 0.352 AC: 53435 AN: 151850 Hom.: 10587 Cov.: 32

Gnomad AFR AF: 0.172

Gnomad AMI AF: 0.361

Gnomad AMR AF: 0.372

Gnomad ASJ AF: 0.366

Gnomad EAS AF: 0.589

Gnomad SAS AF: 0.412

Gnomad FIN AF: 0.498

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.412

Gnomad OTH AF: 0.328

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

GnomAD4 genome AF: 0.352 AC: 53463 AN: 151968 Hom.: 10591 Cov.: 32 AF XY: 0.358 AC XY: 26573 AN XY: 74264

Gnomad4 AFR AF: 0.172

Gnomad4 AMR AF: 0.373

Gnomad4 ASJ AF: 0.366

Gnomad4 EAS AF: 0.588

Gnomad4 SAS AF: 0.411

Gnomad4 FIN AF: 0.498

Gnomad4 NFE AF: 0.412

Gnomad4 OTH AF: 0.327

Alfa AF: 0.399 Hom.: 19801

Bravo AF: 0.334

Asia WGS AF: 0.438 AC: 1523 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	4.8
DANN	Benign	0.70

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

LitVar

Other links and lift over

dbSNP: rs1917527; hg19: chr3-65580498;