1-113683521-G-T

Position:

• chr1-113683521-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 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. 15/20 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

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 Uncertain_significance. Variant got 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/exons	MANE	Protein	UniProt
MAGI3	NM_001142782.2	c.3953G>T	p.Gly1318Val	missense_variant	21/21	ENST00000307546.14	NP_001136254.1
MAGI3	NM_152900.3	c.*1260G>T		3_prime_UTR_variant	21/21		NP_690864.2
MAGI3	XM_005270737.4	c.*666G>T		3_prime_UTR_variant	22/22		XP_005270794.1
MAGI3	XM_017000974.2	c.*634G>T		3_prime_UTR_variant	22/22		XP_016856463.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAGI3	ENST00000307546.14	c.3953G>T	p.Gly1318Val	missense_variant	21/21	5	NM_001142782.2	ENSP00000304604
MAGI3	ENST00000369615.5	c.*666G>T		3_prime_UTR_variant	22/22	5		ENSP00000358628	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

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
MutationTaster	Benign	1.0	N;N
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

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: rs61742849; hg19: chr1-114226143;