1-113568414-A-G

Position:

• chr1-113568414-A-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAGI3	NM_001142782.2	c.434-12128A>G		intron_variant		ENST00000307546.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAGI3	ENST00000307546.14	c.434-12128A>G		intron_variant		5	NM_001142782.2

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

Gnomad4 AFR AF: 0.0879

Gnomad4 AMR AF: 0.357

Gnomad4 ASJ AF: 0.238

Gnomad4 EAS AF: 0.646

Gnomad4 SAS AF: 0.230

Gnomad4 FIN AF: 0.310

Gnomad4 NFE AF: 0.234

Gnomad4 OTH AF: 0.254

Alfa AF: 0.242 Hom.: 2129

Bravo AF: 0.231

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.84
DANN	Benign	0.41

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: rs1343125; hg19: chr1-114111036;