1-113585502-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_001142782.2(MAGI3):c.669G>A(p.Thr223=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00304 in 1,614,008 control chromosomes in the GnomAD database, including 140 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.016 (78 hom., cov: 31)
  • Exomes 𝑓: 0.0017 (62 hom.)
• Consequence: MAGI3 NM_001142782.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.550

Genes affected

MAGI3 (HGNC:29647): (membrane associated guanylate kinase, WW and PDZ domain containing 3) Predicted to enable frizzled binding activity. Predicted to be involved in signal transduction. Predicted to act upstream of or within positive regulation of JUN kinase activity. Located in cell junction. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant 1-113585502-G-A is Benign according to our data. Variant chr1-113585502-G-A is described in ClinVar as [Benign]. Clinvar id is 788941.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.55 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0541 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAGI3	NM_001142782.2	c.669G>A	p.Thr223=	synonymous_variant	4/21	ENST00000307546.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAGI3	ENST00000307546.14	c.669G>A	p.Thr223=	synonymous_variant	4/21	5	NM_001142782.2
MAGI3	ENST00000369617.8	c.669G>A	p.Thr223=	synonymous_variant	4/22	1
MAGI3	ENST00000369611.4	c.669G>A	p.Thr223=	synonymous_variant	4/21	1		P1
MAGI3	ENST00000369615.5	c.669G>A	p.Thr223=	synonymous_variant	4/22	5		P1

Frequencies

GnomAD3 genomes AF: 0.0162 AC: 2465 AN: 152048 Hom.: 78 Cov.: 31

Gnomad AFR AF: 0.0559

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00773

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000579

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.00909

GnomAD3 exomes AF: 0.00429 AC: 1076 AN: 251068 Hom.: 23 AF XY: 0.00290 AC XY: 393 AN XY: 135684

Gnomad AFR exome AF: 0.0572

Gnomad AMR exome AF: 0.00255

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000761

Gnomad SAS exome AF: 0.000229

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000150

Gnomad OTH exome AF: 0.00327

GnomAD4 exome AF: 0.00167 AC: 2436 AN: 1461842 Hom.: 62 Cov.: 31 AF XY: 0.00147 AC XY: 1069 AN XY: 727218

Gnomad4 AFR exome AF: 0.0542

Gnomad4 AMR exome AF: 0.00322

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000277

Gnomad4 SAS exome AF: 0.000243

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000153

Gnomad4 OTH exome AF: 0.00434

GnomAD4 genome AF: 0.0163 AC: 2477 AN: 152166 Hom.: 78 Cov.: 31 AF XY: 0.0157 AC XY: 1167 AN XY: 74394

Gnomad4 AFR AF: 0.0560

Gnomad4 AMR AF: 0.00772

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000580

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000176

Gnomad4 OTH AF: 0.00947

Alfa AF: 0.00714 Hom.: 17

Bravo AF: 0.0184

Asia WGS AF: 0.00462 AC: 16 AN: 3478

EpiCase AF: 0.000327

EpiControl AF: 0.000296

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
Cadd	Benign	3.8
Dann	Benign	0.56

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

LitVar

Other links and lift over

dbSNP: rs35955172; hg19: chr1-114128124;