1-113644533-G-T

Variant names:

• chr1-113644533-G-T
• rs12144215
• NM_001142782.2:c.1998+759G>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.1998+759G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 152,022 control chromosomes in the GnomAD database, including 1,040 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 0.10 (1040 hom., cov: 32)
• Consequence: MAGI3 NM_001142782.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.464
• Publications: 5 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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGI3	NM_001142782.2	c.1998+759G>T		intron_variant	Intron 11 of 20	ENST00000307546.14	NP_001136254.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAGI3	ENST00000307546.14	c.1998+759G>T		intron_variant	Intron 11 of 20	5	NM_001142782.2	ENSP00000304604.9
MAGI3	ENST00000369617.8	c.2073+759G>T		intron_variant	Intron 12 of 21	1		ENSP00000358630.4
MAGI3	ENST00000369611.4	c.1998+759G>T		intron_variant	Intron 11 of 20	1		ENSP00000358624.4
MAGI3	ENST00000369615.5	c.1998+759G>T		intron_variant	Intron 11 of 21	5		ENSP00000358628.1

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15717 AN: 151904 Hom.: 1039 Cov.: 32

Gnomad AFR AF: 0.0254

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.187

Gnomad SAS AF: 0.111

Gnomad FIN AF: 0.142

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.130

Gnomad OTH AF: 0.114

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

GnomAD4 genome AF: 0.103 AC: 15719 AN: 152022 Hom.: 1040 Cov.: 32 AF XY: 0.106 AC XY: 7858 AN XY: 74310

African (AFR) AF: 0.0254 AC: 1053 AN: 41490

American (AMR) AF: 0.126 AC: 1923 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.131 AC: 456 AN: 3470

East Asian (EAS) AF: 0.187 AC: 966 AN: 5160

South Asian (SAS) AF: 0.111 AC: 534 AN: 4814

European-Finnish (FIN) AF: 0.142 AC: 1502 AN: 10564

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.130 AC: 8851 AN: 67970

Other (OTH) AF: 0.118 AC: 248 AN: 2106

Alfa AF: 0.333 Hom.: 3731

Bravo AF: 0.100

Asia WGS AF: 0.166 AC: 577 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.49
DANN	Benign	0.78
PhyloP100		-0.46
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: rs12144215; hg19: chr1-114187155;