rs11102637

Variant names:

• chr1-113449170-G-A
• rs11102637
• NM_001142782.2:c.316+57821G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001142782.2(MAGI3):​c.316+57821G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 151,750 control chromosomes in the GnomAD database, including 3,148 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 0.18 (3148 hom., cov: 31)
• Consequence: MAGI3 NM_001142782.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0550
• Publications: 5 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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.611 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGI3	NM_001142782.2	c.316+57821G>A		intron_variant	Intron 1 of 20	ENST00000307546.14	NP_001136254.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAGI3	ENST00000307546.14	c.316+57821G>A		intron_variant	Intron 1 of 20	5	NM_001142782.2	ENSP00000304604.9

Frequencies

GnomAD3 genomes AF: 0.178 AC: 27025 AN: 151640 Hom.: 3152 Cov.: 31

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.0691

Gnomad AMR AF: 0.235

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.630

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.241

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.197

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

GnomAD4 genome AF: 0.178 AC: 27019 AN: 151750 Hom.: 3148 Cov.: 31 AF XY: 0.184 AC XY: 13612 AN XY: 74172

African (AFR) AF: 0.122 AC: 5055 AN: 41356

American (AMR) AF: 0.235 AC: 3584 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.175 AC: 608 AN: 3466

East Asian (EAS) AF: 0.629 AC: 3247 AN: 5162

South Asian (SAS) AF: 0.146 AC: 702 AN: 4796

European-Finnish (FIN) AF: 0.241 AC: 2531 AN: 10506

Middle Eastern (MID) AF: 0.188 AC: 55 AN: 292

European-Non Finnish (NFE) AF: 0.158 AC: 10757 AN: 67922

Other (OTH) AF: 0.197 AC: 417 AN: 2114

Alfa AF: 0.188 Hom.: 696

Bravo AF: 0.185

Asia WGS AF: 0.329 AC: 1141 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.1
DANN	Benign	0.69
PhyloP100		0.055
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: rs11102637; hg19: chr1-113991792; COSMIC: COSV56831338; COSMIC: COSV56831338;