rs10858004

Variant names:

• chr1-113549684-A-G
• rs10858004
• NM_001142782.2:c.433+53A>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+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
• Publications: 17 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=-0.78).
• 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 rank	MANE	Protein	UniProt
MAGI3	NM_001142782.2	c.433+53A>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+53A>G		intron_variant	Intron 2 of 20	5	NM_001142782.2	ENSP00000304604.9

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

African (AFR) AF: 0.204 AC: 3774 AN: 18512

American (AMR) AF: 0.0968 AC: 2925 AN: 30202

Ashkenazi Jewish (ASJ) AF: 0.220 AC: 4249 AN: 19304

East Asian (EAS) AF: 0.0377 AC: 1301 AN: 34536

South Asian (SAS) AF: 0.214 AC: 11838 AN: 55358

European-Finnish (FIN) AF: 0.173 AC: 8776 AN: 50866

Middle Eastern (MID) AF: 0.183 AC: 739 AN: 4046

European-Non Finnish (NFE) AF: 0.202 AC: 107576 AN: 532150

Other (OTH) AF: 0.186 AC: 6885 AN: 37000

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

African (AFR) AF: 0.213 AC: 8819 AN: 41492

American (AMR) AF: 0.150 AC: 2295 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.223 AC: 775 AN: 3468

East Asian (EAS) AF: 0.0316 AC: 164 AN: 5190

South Asian (SAS) AF: 0.206 AC: 995 AN: 4820

European-Finnish (FIN) AF: 0.153 AC: 1623 AN: 10604

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.210 AC: 14306 AN: 67976

Other (OTH) AF: 0.185 AC: 392 AN: 2116

Alfa AF: 0.203 Hom.: 2769

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
PhyloP100		-0.10
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: rs10858004; hg19: chr1-114092306; COSMIC: COSV56834765;