rs10858002

Positions:

• chr1-113540310-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.317-9205A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 152,140 control chromosomes in the GnomAD database, including 7,375 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 0.29 (7375 hom., cov: 33)
• Consequence: MAGI3 NM_001142782.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0860

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 (EAS) allele frequency at 95% confidence interval = 0.632 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAGI3	NM_001142782.2	c.317-9205A>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.317-9205A>G		intron_variant		5	NM_001142782.2	ENSP00000304604.9

Frequencies

GnomAD3 genomes AF: 0.293 AC: 44580 AN: 152022 Hom.: 7378 Cov.: 33

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.406

Gnomad ASJ AF: 0.279

Gnomad EAS AF: 0.650

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.387

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.310

Gnomad OTH AF: 0.309

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

GnomAD4 genome AF: 0.293 AC: 44587 AN: 152140 Hom.: 7375 Cov.: 33 AF XY: 0.300 AC XY: 22288 AN XY: 74376

Gnomad4 AFR AF: 0.161

Gnomad4 AMR AF: 0.406

Gnomad4 ASJ AF: 0.279

Gnomad4 EAS AF: 0.650

Gnomad4 SAS AF: 0.264

Gnomad4 FIN AF: 0.387

Gnomad4 NFE AF: 0.310

Gnomad4 OTH AF: 0.309

Alfa AF: 0.315 Hom.: 4580

Bravo AF: 0.296

Asia WGS AF: 0.418 AC: 1451 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	7.8
DANN	Benign	0.54

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: rs10858002; hg19: chr1-114082932; COSMIC: COSV56831638;