NM_001142782.2:c.317-6414T>C

Variant names:

• chr1-113543101-T-C
• rs7554019
• NM_001142782.2:c.317-6414T>C

Variant summary

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

The NM_001142782.2(MAGI3):​c.317-6414T>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
• Publications: 7 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.726 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001142782.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAGI3	NM_001142782.2	MANE Select	c.317-6414T>C		intron	N/A	NP_001136254.1
	MAGI3	NM_152900.3		c.317-6414T>C		intron	N/A	NP_690864.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAGI3	ENST00000307546.14	TSL:5 MANE Select	c.317-6414T>C		intron	N/A	ENSP00000304604.9
	MAGI3	ENST00000369617.8	TSL:1	c.317-6414T>C		intron	N/A	ENSP00000358630.4
	MAGI3	ENST00000369611.4	TSL:1	c.317-6414T>C		intron	N/A	ENSP00000358624.4

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

African (AFR) AF: 0.251 AC: 10410 AN: 41440

American (AMR) AF: 0.645 AC: 9834 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.599 AC: 2080 AN: 3472

East Asian (EAS) AF: 0.746 AC: 3847 AN: 5160

South Asian (SAS) AF: 0.652 AC: 3137 AN: 4812

European-Finnish (FIN) AF: 0.672 AC: 7030 AN: 10454

Middle Eastern (MID) AF: 0.606 AC: 177 AN: 292

European-Non Finnish (NFE) AF: 0.622 AC: 42267 AN: 67940

Other (OTH) AF: 0.569 AC: 1197 AN: 2104

Alfa AF: 0.594 Hom.: 106612

Bravo AF: 0.521

Asia WGS AF: 0.653 AC: 2269 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.71
DANN	Benign	0.52
PhyloP100		-0.42
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: rs7554019; hg19: chr1-114085723; COSMIC: COSV56831654;