rs10858004

Positions:

• chr1-113549684-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.433+53A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 934,138 control chromosomes in the GnomAD database, including 18,517 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 0.20 (3106 hom., cov: 32)
  • Exomes 𝑓: 0.19 (15411 hom.)
• Consequence: MAGI3 NM_001142782.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.103

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=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.209 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAGI3	NM_001142782.2	c.433+53A>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.433+53A>G		intron_variant		5	NM_001142782.2	ENSP00000304604

Frequencies

GnomAD3 genomes AF: 0.195 AC: 29696 AN: 152046 Hom.: 3102 Cov.: 32

Gnomad AFR AF: 0.213

Gnomad AMI AF: 0.303

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.223

Gnomad EAS AF: 0.0315

Gnomad SAS AF: 0.207

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.210

Gnomad OTH AF: 0.187

GnomAD4 exome AF: 0.189 AC: 148063 AN: 781974 Hom.: 15411 AF XY: 0.191 AC XY: 77929 AN XY: 407822

Gnomad4 AFR exome AF: 0.204

Gnomad4 AMR exome AF: 0.0968

Gnomad4 ASJ exome AF: 0.220

Gnomad4 EAS exome AF: 0.0377

Gnomad4 SAS exome AF: 0.214

Gnomad4 FIN exome AF: 0.173

Gnomad4 NFE exome AF: 0.202

Gnomad4 OTH exome AF: 0.186

GnomAD4 genome AF: 0.195 AC: 29703 AN: 152164 Hom.: 3106 Cov.: 32 AF XY: 0.192 AC XY: 14264 AN XY: 74400

Gnomad4 AFR AF: 0.213

Gnomad4 AMR AF: 0.150

Gnomad4 ASJ AF: 0.223

Gnomad4 EAS AF: 0.0316

Gnomad4 SAS AF: 0.206

Gnomad4 FIN AF: 0.153

Gnomad4 NFE AF: 0.210

Gnomad4 OTH AF: 0.185

Alfa AF: 0.202 Hom.: 2344

Bravo AF: 0.190

Asia WGS AF: 0.120 AC: 419 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	2.2
DANN	Benign	0.83

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: rs10858004; hg19: chr1-114092306; COSMIC: COSV56834765;