3-65364931-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM1 PM2 BP4

The NM_001033057.2(MAGI1):c.3212C>A(p.Thr1071Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,736 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: MAGI1 NM_001033057.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.12

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 3 ACMG points.

• PM1: In a modified_residue Phosphoserine (size 0) in uniprot entity MAGI1_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3049153).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAGI1	NM_001033057.2	c.3212C>A	p.Thr1071Asn	missense_variant	19/23	ENST00000402939.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAGI1	ENST00000402939.7	c.3212C>A	p.Thr1071Asn	missense_variant	19/23	1	NM_001033057.2	A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461736 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727170

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: 0.00000360

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

Jan 23, 2023

The c.3212C>A (p.T1071N) alteration is located in exon 19 (coding exon 19) of the MAGI1 gene. This alteration results from a C to A substitution at nucleotide position 3212, causing the threonine (T) at amino acid position 1071 to be replaced by an asparagine (N). 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	-0.18	T
BayesDel_noAF	Benign	-0.49
Cadd	Uncertain	23
Dann	Uncertain	0.98
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Pathogenic	0.99	D
M_CAP	Benign	0.058	D
MetaRNN	Benign	0.30	T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-1.9	N;.;.;N;N;N;N;N
REVEL	Benign	0.13
Sift	Benign	0.071	T;.;.;T;T;T;T;T
Sift4G	Uncertain	0.043	D;T;T;D;T;D;T;T
Polyphen		0.73	P;.;.;P;.;P;B;.
Vest4		0.37
MutPred		0.25		Loss of stability (P = 0.0439);.;.;.;.;.;.;.;
MVP		0.36
MPC		1.1
ClinPred		0.93	D
GERP RS		6.2
gMVP		0.21

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-65350606;