1-113537449-C-T

Variant names:

• chr1-113537449-C-T
• rs2153977
• NM_001142782.2:c.317-12066C>T

Variant summary

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

The NM_001142782.2(MAGI3):​c.317-12066C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 152,022 control chromosomes in the GnomAD database, including 7,283 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 (7283 hom., cov: 32)
• Consequence: MAGI3 NM_001142782.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.121
• Publications: 18 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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.629 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGI3	NM_001142782.2	c.317-12066C>T		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.317-12066C>T		intron_variant	Intron 1 of 20	5	NM_001142782.2	ENSP00000304604.9

Frequencies

GnomAD3 genomes AF: 0.291 AC: 44205 AN: 151904 Hom.: 7285 Cov.: 32

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.405

Gnomad ASJ AF: 0.275

Gnomad EAS AF: 0.648

Gnomad SAS AF: 0.261

Gnomad FIN AF: 0.386

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.308

Gnomad OTH AF: 0.309

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

GnomAD4 genome AF: 0.291 AC: 44213 AN: 152022 Hom.: 7283 Cov.: 32 AF XY: 0.297 AC XY: 22086 AN XY: 74284

African (AFR) AF: 0.157 AC: 6516 AN: 41498

American (AMR) AF: 0.405 AC: 6186 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.275 AC: 954 AN: 3468

East Asian (EAS) AF: 0.648 AC: 3330 AN: 5142

South Asian (SAS) AF: 0.261 AC: 1259 AN: 4820

European-Finnish (FIN) AF: 0.386 AC: 4064 AN: 10530

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.308 AC: 20928 AN: 67970

Other (OTH) AF: 0.309 AC: 652 AN: 2112

Alfa AF: 0.302 Hom.: 30639

Bravo AF: 0.294

Asia WGS AF: 0.403 AC: 1401 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	8.8
DANN	Benign	0.77
PhyloP100		-0.12
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: rs2153977; hg19: chr1-114080071;