1-113520970-A-G

Variant names:

• chr1-113520970-A-G
• rs6694861
• NM_001142782.2:c.317-28545A>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.317-28545A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.545 in 151,942 control chromosomes in the GnomAD database, including 23,881 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 0.55 (23881 hom., cov: 31)
• Consequence: MAGI3 NM_001142782.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.499
• Publications: 3 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.714 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.317-28545A>G		intron	N/A	NP_001136254.1
	MAGI3	NM_152900.3		c.317-28545A>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.317-28545A>G		intron	N/A	ENSP00000304604.9
	MAGI3	ENST00000369617.8	TSL:1	c.317-28545A>G		intron	N/A	ENSP00000358630.4
	MAGI3	ENST00000369611.4	TSL:1	c.317-28545A>G		intron	N/A	ENSP00000358624.4

Frequencies

GnomAD3 genomes AF: 0.545 AC: 82752 AN: 151824 Hom.: 23841 Cov.: 31

Gnomad AFR AF: 0.721

Gnomad AMI AF: 0.640

Gnomad AMR AF: 0.476

Gnomad ASJ AF: 0.475

Gnomad EAS AF: 0.183

Gnomad SAS AF: 0.602

Gnomad FIN AF: 0.422

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.500

Gnomad OTH AF: 0.494

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

GnomAD4 genome AF: 0.545 AC: 82847 AN: 151942 Hom.: 23881 Cov.: 31 AF XY: 0.539 AC XY: 40057 AN XY: 74268

African (AFR) AF: 0.721 AC: 29858 AN: 41430

American (AMR) AF: 0.477 AC: 7280 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.475 AC: 1650 AN: 3472

East Asian (EAS) AF: 0.184 AC: 953 AN: 5174

South Asian (SAS) AF: 0.601 AC: 2895 AN: 4814

European-Finnish (FIN) AF: 0.422 AC: 4454 AN: 10546

Middle Eastern (MID) AF: 0.558 AC: 164 AN: 294

European-Non Finnish (NFE) AF: 0.500 AC: 33971 AN: 67928

Other (OTH) AF: 0.493 AC: 1038 AN: 2104

Alfa AF: 0.526 Hom.: 4529

Bravo AF: 0.549

Asia WGS AF: 0.441 AC: 1535 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.4
DANN	Benign	0.72
PhyloP100		-0.50
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: rs6694861; hg19: chr1-114063592;