rs6694861

Positions:

• chr1-113520970-A-G
• chr1-113520970-A-T

Variant summary

Our verdict is Benign. Variant got -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

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]

MAGI3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAGI3	NM_001142782.2	c.317-28545A>G		intron_variant		ENST00000307546.14	NP_001136254.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAGI3	ENST00000307546.14	c.317-28545A>G		intron_variant		5	NM_001142782.2	ENSP00000304604.9

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

Gnomad4 AFR AF: 0.721

Gnomad4 AMR AF: 0.477

Gnomad4 ASJ AF: 0.475

Gnomad4 EAS AF: 0.184

Gnomad4 SAS AF: 0.601

Gnomad4 FIN AF: 0.422

Gnomad4 NFE AF: 0.500

Gnomad4 OTH AF: 0.493

Alfa AF: 0.507 Hom.: 3476

Bravo AF: 0.549

Asia WGS AF: 0.441 AC: 1535 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.4
DANN	Benign	0.72

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: rs6694861; hg19: chr1-114063592;