1-113642968-A-G

Position:

• chr1-113642968-A-G

Variant summary

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

The NM_001142782.2(MAGI3):​c.1966+452A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.806 in 152,232 control chromosomes in the GnomAD database, including 50,600 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 0.81 (50600 hom., cov: 34)
• Consequence: MAGI3 NM_001142782.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0120

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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.948 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAGI3	NM_001142782.2	c.1966+452A>G		intron_variant		ENST00000307546.14	NP_001136254.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAGI3	ENST00000307546.14	c.1966+452A>G		intron_variant		5	NM_001142782.2	ENSP00000304604.9
MAGI3	ENST00000369617.8	c.2041+452A>G		intron_variant		1		ENSP00000358630.4
MAGI3	ENST00000369611.4	c.1966+452A>G		intron_variant		1		ENSP00000358624.4
MAGI3	ENST00000369615.5	c.1966+452A>G		intron_variant		5		ENSP00000358628.1

Frequencies

GnomAD3 genomes AF: 0.806 AC: 122648 AN: 152114 Hom.: 50540 Cov.: 34

Gnomad AFR AF: 0.956

Gnomad AMI AF: 0.848

Gnomad AMR AF: 0.734

Gnomad ASJ AF: 0.801

Gnomad EAS AF: 0.376

Gnomad SAS AF: 0.818

Gnomad FIN AF: 0.695

Gnomad MID AF: 0.775

Gnomad NFE AF: 0.781

Gnomad OTH AF: 0.783

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

GnomAD4 genome AF: 0.806 AC: 122767 AN: 152232 Hom.: 50600 Cov.: 34 AF XY: 0.801 AC XY: 59589 AN XY: 74418

Gnomad4 AFR AF: 0.956

Gnomad4 AMR AF: 0.734

Gnomad4 ASJ AF: 0.801

Gnomad4 EAS AF: 0.376

Gnomad4 SAS AF: 0.818

Gnomad4 FIN AF: 0.695

Gnomad4 NFE AF: 0.781

Gnomad4 OTH AF: 0.782

Alfa AF: 0.782 Hom.: 28559

Bravo AF: 0.807

Asia WGS AF: 0.656 AC: 2282 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.1
DANN	Benign	0.69

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: rs1230661; hg19: chr1-114185590;