1-113674905-T-C

Position:

• chr1-113674905-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.3189+1440T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.24 in 152,090 control chromosomes in the GnomAD database, including 4,873 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 0.24 (4873 hom., cov: 32)
• Consequence: MAGI3 NM_001142782.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0860

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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.374 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAGI3	NM_001142782.2	c.3189+1440T>C		intron_variant		ENST00000307546.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAGI3	ENST00000307546.14	c.3189+1440T>C		intron_variant		5	NM_001142782.2
MAGI3	ENST00000369611.4	c.3189+1440T>C		intron_variant		1		P1
MAGI3	ENST00000369617.8	c.3264+1440T>C		intron_variant		1
MAGI3	ENST00000369615.5	c.3189+1440T>C		intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.240 AC: 36461 AN: 151972 Hom.: 4872 Cov.: 32

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.292

Gnomad AMR AF: 0.240

Gnomad ASJ AF: 0.297

Gnomad EAS AF: 0.0909

Gnomad SAS AF: 0.389

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.297

Gnomad OTH AF: 0.257

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

GnomAD4 genome AF: 0.240 AC: 36483 AN: 152090 Hom.: 4873 Cov.: 32 AF XY: 0.239 AC XY: 17793 AN XY: 74334

Gnomad4 AFR AF: 0.137

Gnomad4 AMR AF: 0.241

Gnomad4 ASJ AF: 0.297

Gnomad4 EAS AF: 0.0909

Gnomad4 SAS AF: 0.389

Gnomad4 FIN AF: 0.249

Gnomad4 NFE AF: 0.297

Gnomad4 OTH AF: 0.257

Alfa AF: 0.289 Hom.: 11133

Bravo AF: 0.232

Asia WGS AF: 0.239 AC: 833 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.1
DANN	Benign	0.63

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: rs17274634; hg19: chr1-114217527;