chr3-65364720-G-C

Position:

• chr3-65364720-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001033057.2(MAGI1):​c.3296C>G​(p.Thr1099Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 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: MAGI1 NM_001033057.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.79

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

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=0.10723752).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAGI1	NM_001033057.2	c.3296C>G	p.Thr1099Ser	missense_variant	20/23	ENST00000402939.7	NP_001028229.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAGI1	ENST00000402939.7	c.3296C>G	p.Thr1099Ser	missense_variant	20/23	1	NM_001033057.2	ENSP00000385450.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

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

Jul 16, 2024

The c.3296C>G (p.T1099S) alteration is located in exon 20 (coding exon 20) of the MAGI1 gene. This alteration results from a C to G substitution at nucleotide position 3296, causing the threonine (T) at amino acid position 1099 to be replaced by a serine (S). 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	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Uncertain	24
DANN	Benign	0.92
DEOGEN2	Benign	0.048	.;.;T;.;.;.;.;.
Eigen	Benign	-0.19
Eigen_PC	Benign	0.051
FATHMM_MKL	Uncertain	0.94	D
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.11	T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.20	.;.;.;.;.;N;.;.
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.41	N;.;.;N;N;N;N;N
REVEL	Benign	0.087
Sift	Benign	0.57	T;.;.;T;T;T;T;T
Sift4G	Benign	0.73	T;T;T;T;T;T;T;T
Polyphen		0.0	B;.;.;B;.;B;B;.
Vest4		0.074
MutPred		0.20		Loss of glycosylation at T1127 (P = 0.033);.;.;.;.;.;.;.;
MVP		0.19
MPC		0.50
ClinPred		0.88	D
GERP RS		4.1
gMVP		0.12

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.20		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.20		Position offset: -1

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

Publications

LitVar

Other links and lift over

dbSNP: rs1053443162; hg19: chr3-65350395;