3-65356662-G-A

Variant summary

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

The NM_001033057.2(MAGI1):c.4105C>T(p.Arg1369Trp) 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. 10/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MAGI1 NM_001033057.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.26

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=0.2321204).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAGI1	NM_001033057.2	c.4105C>T	p.Arg1369Trp	missense_variant	23/23	ENST00000402939.7
MAGI1	NM_001365903.2	c.*414C>T		3_prime_UTR_variant	25/25
MAGI1	NM_001365904.2	c.*414C>T		3_prime_UTR_variant	25/25
MAGI1	NM_015520.2	c.*414C>T		3_prime_UTR_variant	25/25

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAGI1	ENST00000402939.7	c.4105C>T	p.Arg1369Trp	missense_variant	23/23	1	NM_001033057.2	A2
MAGI1	ENST00000621418.4	c.3184C>T	p.Arg1062Trp	missense_variant	22/22	1
MAGI1	ENST00000330909.12	c.*414C>T		3_prime_UTR_variant	25/25	1		P4
MAGI1	ENST00000611645.4	c.*414C>T		3_prime_UTR_variant	24/24	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1431478 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 709914

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

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 26, 2021

The c.4105C>T (p.R1369W) alteration is located in exon 23 (coding exon 23) of the MAGI1 gene. This alteration results from a C to T substitution at nucleotide position 4105, causing the arginine (R) at amino acid position 1369 to be replaced by a tryptophan (W). 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	-0.16	T
BayesDel_noAF	Benign	-0.47
Cadd	Uncertain	25
Dann	Uncertain	1.0
Eigen	Benign	0.026
Eigen_PC	Benign	-0.0046
FATHMM_MKL	Uncertain	0.81	D
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.23	T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	0.58	D;D
PrimateAI	Benign	0.46	T
Sift4G	Uncertain	0.0020	D;D
Polyphen		0.99	.;D
Vest4		0.33
MutPred		0.33		.;Loss of helix (P = 0.1706);
MVP		0.24
MPC		0.58
ClinPred		0.89	D
GERP RS		3.3
gMVP		0.49

Splicing

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: chr3-65342337;