1-113568414-A-G

Variant names:

• chr1-113568414-A-G
• rs1343125
• NM_001142782.2:c.434-12128A>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.434-12128A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 151,982 control chromosomes in the GnomAD database, including 4,922 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 0.23 (4922 hom., cov: 32)
• Consequence: MAGI3 NM_001142782.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0920
• Publications: 10 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.628 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001142782.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAGI3	NM_001142782.2	MANE Select	c.434-12128A>G		intron	N/A	NP_001136254.1
	MAGI3	NM_152900.3		c.434-12128A>G		intron	N/A	NP_690864.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAGI3	ENST00000307546.14	TSL:5 MANE Select	c.434-12128A>G		intron	N/A	ENSP00000304604.9
	MAGI3	ENST00000369617.8	TSL:1	c.434-12128A>G		intron	N/A	ENSP00000358630.4
	MAGI3	ENST00000369611.4	TSL:1	c.434-12128A>G		intron	N/A	ENSP00000358624.4

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34342 AN: 151862 Hom.: 4925 Cov.: 32

Gnomad AFR AF: 0.0881

Gnomad AMI AF: 0.205

Gnomad AMR AF: 0.357

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.646

Gnomad SAS AF: 0.230

Gnomad FIN AF: 0.310

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.234

Gnomad OTH AF: 0.254

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

GnomAD4 genome AF: 0.226 AC: 34344 AN: 151982 Hom.: 4922 Cov.: 32 AF XY: 0.233 AC XY: 17337 AN XY: 74266

African (AFR) AF: 0.0879 AC: 3653 AN: 41546

American (AMR) AF: 0.357 AC: 5449 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.238 AC: 826 AN: 3470

East Asian (EAS) AF: 0.646 AC: 3340 AN: 5170

South Asian (SAS) AF: 0.230 AC: 1111 AN: 4824

European-Finnish (FIN) AF: 0.310 AC: 3265 AN: 10546

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.234 AC: 15901 AN: 67846

Other (OTH) AF: 0.254 AC: 536 AN: 2108

Alfa AF: 0.239 Hom.: 3304

Bravo AF: 0.231

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.84
DANN	Benign	0.41
PhyloP100		-0.092
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: rs1343125; hg19: chr1-114111036;