rs7554019

Positions:

• chr1-113543101-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001142782.2(MAGI3):​c.317-6414T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.53 in 151,820 control chromosomes in the GnomAD database, including 23,760 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 0.53 (23760 hom., cov: 32)
• Consequence: MAGI3 NM_001142782.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.425

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.726 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAGI3	NM_001142782.2	c.317-6414T>C		intron_variant		ENST00000307546.14	NP_001136254.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAGI3	ENST00000307546.14	c.317-6414T>C		intron_variant		5	NM_001142782.2	ENSP00000304604

Frequencies

GnomAD3 genomes AF: 0.530 AC: 80480 AN: 151714 Hom.: 23765 Cov.: 32

Gnomad AFR AF: 0.252

Gnomad AMI AF: 0.558

Gnomad AMR AF: 0.645

Gnomad ASJ AF: 0.599

Gnomad EAS AF: 0.746

Gnomad SAS AF: 0.652

Gnomad FIN AF: 0.672

Gnomad MID AF: 0.599

Gnomad NFE AF: 0.622

Gnomad OTH AF: 0.569

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

GnomAD4 genome AF: 0.530 AC: 80485 AN: 151820 Hom.: 23760 Cov.: 32 AF XY: 0.537 AC XY: 39832 AN XY: 74204

Gnomad4 AFR AF: 0.251

Gnomad4 AMR AF: 0.645

Gnomad4 ASJ AF: 0.599

Gnomad4 EAS AF: 0.746

Gnomad4 SAS AF: 0.652

Gnomad4 FIN AF: 0.672

Gnomad4 NFE AF: 0.622

Gnomad4 OTH AF: 0.569

Alfa AF: 0.612 Hom.: 49976

Bravo AF: 0.521

Asia WGS AF: 0.653 AC: 2269 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.71
DANN	Benign	0.52

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: rs7554019; hg19: chr1-114085723; COSMIC: COSV56831654;