3-65375945-C-A

Variant names:

• chr3-65375945-C-A
• ENST00000483466.5:c.3083G>T

Variant summary

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

The NM_001033057.2(MAGI1):​c.2996G>T​(p.Gly999Val) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MAGI1 NM_001033057.2 missense, splice_region
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.57
• Publications: 0 publications found

Genes affected

MAGI1 (HGNC:946): (membrane associated guanylate kinase, WW and PDZ domain containing 1) The protein encoded by this gene is a member of the membrane-associated guanylate kinase homologue (MAGUK) family. MAGUK proteins participate in the assembly of multiprotein complexes on the inner surface of the plasma membrane at regions of cell-cell contact. The product of this gene may play a role as scaffolding protein at cell-cell junctions. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

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_001033057.2. 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
	MAGI1	NM_001033057.2	MANE Select	c.2996G>T	p.Gly999Val	missense splice_region	Exon 18 of 23	NP_001028229.1	Q96QZ7-2
	MAGI1	NM_001365903.2		c.3086G>T	p.Gly1029Val	missense	Exon 19 of 25	NP_001352832.1
	MAGI1	NM_001365905.1		c.3086G>T	p.Gly1029Val	missense	Exon 19 of 23	NP_001352834.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAGI1	ENST00000483466.5	TSL:1	c.3083G>T	p.Gly1028Val	missense	Exon 19 of 23	ENSP00000420323.1	Q96QZ7-3
	MAGI1	ENST00000402939.7	TSL:1 MANE Select	c.2996G>T	p.Gly999Val	missense splice_region	Exon 18 of 23	ENSP00000385450.2	Q96QZ7-2
	MAGI1	ENST00000330909.12	TSL:1	c.3080G>T	p.Gly1027Val	missense splice_region	Exon 19 of 25	ENSP00000331157.7	Q96QZ7-5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.81
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.091	T
Eigen	Uncertain	0.64
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Pathogenic	1.0	D
M_CAP	Benign	0.039	D
MetaRNN	Uncertain	0.66	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
PhyloP100		7.6
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-2.2	N
REVEL	Uncertain	0.36
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.051	T
Polyphen		0.35	B
Vest4		0.85
MutPred		0.50		Loss of disorder (P = 0.0793)
MVP		0.51
MPC		1.7
ClinPred		0.95	D
GERP RS		6.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.73
Mutation Taster		=31/69	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.17		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

hg19: chr3-65361620; COSMIC: COSV100441461; COSMIC: COSV100441461;