rs12030900

Variant names:

• chr1-113431641-A-G
• rs12030900
• NM_001142782.2:c.316+40292A>G

Variant summary

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

The NM_001142782.2(MAGI3):​c.316+40292A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 152,138 control chromosomes in the GnomAD database, including 3,152 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 0.18 (3152 hom., cov: 32)
• Consequence: MAGI3 NM_001142782.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00200
• Publications: 7 publications found

Genes affected

MAGI3 (HGNC:29647): (membrane associated guanylate kinase, WW and PDZ domain containing 3) Predicted to enable frizzled binding activity. Predicted to be involved in signal transduction. Predicted to act upstream of or within positive regulation of JUN kinase activity. Located in cell junction. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.607 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGI3	NM_001142782.2	c.316+40292A>G		intron_variant	Intron 1 of 20	ENST00000307546.14	NP_001136254.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAGI3	ENST00000307546.14	c.316+40292A>G		intron_variant	Intron 1 of 20	5	NM_001142782.2	ENSP00000304604.9

Frequencies

GnomAD3 genomes AF: 0.179 AC: 27156 AN: 152020 Hom.: 3156 Cov.: 32

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.0692

Gnomad AMR AF: 0.235

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.626

Gnomad SAS AF: 0.147

Gnomad FIN AF: 0.242

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.198

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

GnomAD4 genome AF: 0.178 AC: 27155 AN: 152138 Hom.: 3152 Cov.: 32 AF XY: 0.184 AC XY: 13681 AN XY: 74370

African (AFR) AF: 0.124 AC: 5155 AN: 41538

American (AMR) AF: 0.235 AC: 3593 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.175 AC: 608 AN: 3468

East Asian (EAS) AF: 0.625 AC: 3236 AN: 5176

South Asian (SAS) AF: 0.147 AC: 709 AN: 4830

European-Finnish (FIN) AF: 0.242 AC: 2551 AN: 10554

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.158 AC: 10767 AN: 67982

Other (OTH) AF: 0.198 AC: 418 AN: 2114

Alfa AF: 0.177 Hom.: 1526

Bravo AF: 0.185

Asia WGS AF: 0.329 AC: 1135 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.4
DANN	Benign	0.62
PhyloP100		0.0020
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: rs12030900; hg19: chr1-113974263; COSMIC: COSV56831284;