3-65379530-G-A

Position:

• chr3-65379530-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001033057.2(MAGI1):​c.2726C>T​(p.Pro909Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MAGI1 NM_001033057.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.67

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]

MAGI1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAGI1	NM_001033057.2	c.2726C>T	p.Pro909Leu	missense_variant	17/23	ENST00000402939.7	NP_001028229.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAGI1	ENST00000402939.7	c.2726C>T	p.Pro909Leu	missense_variant	17/23	1	NM_001033057.2	ENSP00000385450.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 01, 2024

The c.2726C>T (p.P909L) alteration is located in exon 17 (coding exon 17) of the MAGI1 gene. This alteration results from a C to T substitution at nucleotide position 2726, causing the proline (P) at amino acid position 909 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.051	T
BayesDel_noAF	Benign	-0.16
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	.;.;T;.;.;.;.;.
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Pathogenic	0.99	D
M_CAP	Benign	0.049	D
MetaRNN	Uncertain	0.51	D;D;D;D;D;D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L;.;.;.;.;L;.;.
PrimateAI	Uncertain	0.71	T
PROVEAN	Pathogenic	-5.4	D;.;.;D;D;D;D;D
REVEL	Benign	0.25
Sift	Uncertain	0.024	D;.;.;D;D;D;D;D
Sift4G	Uncertain	0.025	D;D;D;D;D;D;D;D
Polyphen		0.018	B;.;.;B;.;B;P;.
Vest4		0.81
MutPred		0.19		Loss of glycosylation at S938 (P = 0.0634);.;.;.;.;Loss of glycosylation at S938 (P = 0.0634);.;.;
MVP		0.34
MPC		0.81
ClinPred		0.99	D
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.49

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-65365205;