1-113683521-G-T

Variant names:

• chr1-113683521-G-T
• rs61742849
• NM_001142782.2:c.3953G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001142782.2(MAGI3):​c.3953G>T​(p.Gly1318Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MAGI3 NM_001142782.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.225
• Publications: 21 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08016217).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGI3	NM_001142782.2	c.3953G>T	p.Gly1318Val	missense_variant	Exon 21 of 21	ENST00000307546.14	NP_001136254.1
MAGI3	NM_152900.3	c.*1260G>T		3_prime_UTR_variant	Exon 21 of 21		NP_690864.2
MAGI3	XM_017000974.2	c.*634G>T		3_prime_UTR_variant	Exon 22 of 22		XP_016856463.1
MAGI3	XM_005270737.4	c.*666G>T		3_prime_UTR_variant	Exon 22 of 22		XP_005270794.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAGI3	ENST00000307546.14	c.3953G>T	p.Gly1318Val	missense_variant	Exon 21 of 21	5	NM_001142782.2	ENSP00000304604.9
MAGI3	ENST00000369615.5	c.*666G>T		3_prime_UTR_variant	Exon 22 of 22	5		ENSP00000358628.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 267

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	15
DANN	Benign	0.93
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.53	T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.080	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.23
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.035
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0070	D
Vest4		0.14
MutPred		0.20		Loss of catalytic residue at A1317 (P = 0.0593);
MVP		0.11
MPC		0.20
ClinPred		0.22	T
GERP RS		2.2
Varity_R		0.088
gMVP		0.31
Mutation Taster		=95/5	polymorphism

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: rs61742849; hg19: chr1-114226143;