1-113391308-G-C

Variant names:

• chr1-113391308-G-C
• rs1193797245
• NM_001142782.2:c.275G>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001142782.2(MAGI3):​c.275G>C​(p.Arg92Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R92L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MAGI3 NM_001142782.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.44
• Publications: 0 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]

ENSG00000303143 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAGI3	NM_001142782.2	MANE Select	c.275G>C	p.Arg92Pro	missense	Exon 1 of 21	NP_001136254.1	Q5TCQ9-4
	MAGI3	NM_152900.3		c.275G>C	p.Arg92Pro	missense	Exon 1 of 21	NP_690864.2	Q5TCQ9-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAGI3	ENST00000307546.14	TSL:5 MANE Select	c.275G>C	p.Arg92Pro	missense	Exon 1 of 21	ENSP00000304604.9	Q5TCQ9-4
	MAGI3	ENST00000369617.8	TSL:1	c.275G>C	p.Arg92Pro	missense	Exon 1 of 22	ENSP00000358630.4	Q5TCQ9-2
	MAGI3	ENST00000369611.4	TSL:1	c.275G>C	p.Arg92Pro	missense	Exon 1 of 21	ENSP00000358624.4	Q5TCQ9-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 218590 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.0
CADD	Pathogenic	33
DANN	Uncertain	1.0
DEOGEN2	Benign	0.34	T
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Benign	0.72	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.048	D
MetaRNN	Uncertain	0.66	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		6.4
PrimateAI	Uncertain	0.72	T
PROVEAN	Uncertain	-2.7	D
REVEL	Uncertain	0.30
Sift	Uncertain	0.029	D
Sift4G	Uncertain	0.025	D
Polyphen		1.0	D
Vest4		0.66
MutPred		0.57		Loss of MoRF binding (P = 5e-04)
MVP		0.37
MPC		2.7
ClinPred		0.98	D
GERP RS		3.4
PromoterAI		0.0044	Neutral
Varity_R		0.80
gMVP		0.94
Mutation Taster		=43/57	disease causing

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: rs1193797245; hg19: chr1-113933930;