1-113553475-T-G

Variant names:

• chr1-113553475-T-G
• rs12035317
• NM_001142782.2:c.433+3844T>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.433+3844T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 152,064 control chromosomes in the GnomAD database, including 4,946 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 0.23 (4946 hom., cov: 32)
• Consequence: MAGI3 NM_001142782.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.173
• Publications: 9 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=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.63 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGI3	NM_001142782.2	c.433+3844T>G		intron_variant	Intron 2 of 20	ENST00000307546.14	NP_001136254.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAGI3	ENST00000307546.14	c.433+3844T>G		intron_variant	Intron 2 of 20	5	NM_001142782.2	ENSP00000304604.9

Frequencies

GnomAD3 genomes AF: 0.225 AC: 34228 AN: 151944 Hom.: 4948 Cov.: 32

Gnomad AFR AF: 0.0835

Gnomad AMI AF: 0.207

Gnomad AMR AF: 0.355

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.649

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.311

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.235

Gnomad OTH AF: 0.255

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

GnomAD4 genome AF: 0.225 AC: 34229 AN: 152064 Hom.: 4946 Cov.: 32 AF XY: 0.233 AC XY: 17303 AN XY: 74320

African (AFR) AF: 0.0833 AC: 3458 AN: 41506

American (AMR) AF: 0.355 AC: 5423 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.237 AC: 824 AN: 3470

East Asian (EAS) AF: 0.649 AC: 3351 AN: 5166

South Asian (SAS) AF: 0.231 AC: 1110 AN: 4802

European-Finnish (FIN) AF: 0.311 AC: 3284 AN: 10558

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.235 AC: 15975 AN: 67968

Other (OTH) AF: 0.254 AC: 538 AN: 2114

Alfa AF: 0.239 Hom.: 5168

Bravo AF: 0.230

Asia WGS AF: 0.383 AC: 1331 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	2.3
DANN	Benign	0.76
PhyloP100		0.17
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: rs12035317; hg19: chr1-114096097;