NM_001033057.2:c.430+19889G>T

Variant names:

• chr3-65602083-C-A
• rs7629574
• NM_001033057.2:c.430+19889G>T

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+19889G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 151,878 control chromosomes in the GnomAD database, including 5,610 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 0.27 (5610 hom., cov: 32)
• Consequence: MAGI1 NM_001033057.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.43
• Publications: 4 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.3 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGI1	NM_001033057.2	c.430+19889G>T		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+19889G>T		intron_variant	Intron 2 of 22	1	NM_001033057.2	ENSP00000385450.2

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40240 AN: 151760 Hom.: 5600 Cov.: 32

Gnomad AFR AF: 0.305

Gnomad AMI AF: 0.285

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.240

Gnomad EAS AF: 0.0216

Gnomad SAS AF: 0.0988

Gnomad FIN AF: 0.274

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.278

Gnomad OTH AF: 0.248

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

GnomAD4 genome AF: 0.265 AC: 40291 AN: 151878 Hom.: 5610 Cov.: 32 AF XY: 0.259 AC XY: 19239 AN XY: 74222

African (AFR) AF: 0.305 AC: 12632 AN: 41432

American (AMR) AF: 0.237 AC: 3623 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.240 AC: 831 AN: 3466

East Asian (EAS) AF: 0.0217 AC: 112 AN: 5170

South Asian (SAS) AF: 0.0986 AC: 474 AN: 4806

European-Finnish (FIN) AF: 0.274 AC: 2890 AN: 10536

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.278 AC: 18897 AN: 67890

Other (OTH) AF: 0.245 AC: 515 AN: 2102

Alfa AF: 0.262 Hom.: 6833

Bravo AF: 0.265

Asia WGS AF: 0.0860 AC: 300 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.39
DANN	Benign	0.36
PhyloP100		-1.4
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: rs7629574; hg19: chr3-65587758;