1-113391308-G-T

Variant names:

• chr1-113391308-G-T
• rs1193797245
• NM_001142782.2:c.275G>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001142782.2(MAGI3):​c.275G>T​(p.Arg92Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000415 in 1,444,824 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000042 (0 hom.)
• Consequence: MAGI3 NM_001142782.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.44
• Publications: 0 publications found

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]

ENSG00000303143 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 6 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001142782.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAGI3	NM_001142782.2	MANE Select	c.275G>T	p.Arg92Leu	missense	Exon 1 of 21	NP_001136254.1	Q5TCQ9-4
	MAGI3	NM_152900.3		c.275G>T	p.Arg92Leu	missense	Exon 1 of 21	NP_690864.2	Q5TCQ9-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAGI3	ENST00000307546.14	TSL:5 MANE Select	c.275G>T	p.Arg92Leu	missense	Exon 1 of 21	ENSP00000304604.9	Q5TCQ9-4
	MAGI3	ENST00000369617.8	TSL:1	c.275G>T	p.Arg92Leu	missense	Exon 1 of 22	ENSP00000358630.4	Q5TCQ9-2
	MAGI3	ENST00000369611.4	TSL:1	c.275G>T	p.Arg92Leu	missense	Exon 1 of 21	ENSP00000358624.4	Q5TCQ9-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000415 AC: 6 AN: 1444824 Hom.: 0 Cov.: 31 AF XY: 0.00000836 AC XY: 6 AN XY: 717322

African (AFR) AF: 0.00 AC: 0 AN: 32970

American (AMR) AF: 0.00 AC: 0 AN: 42966

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25828

East Asian (EAS) AF: 0.00 AC: 0 AN: 38340

South Asian (SAS) AF: 0.00 AC: 0 AN: 83532

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50972

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5752

European-Non Finnish (NFE) AF: 0.00000543 AC: 6 AN: 1104792

Other (OTH) AF: 0.00 AC: 0 AN: 59672

GnomAD4 genome Cov.: 32

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.76
BayesDel_addAF	Uncertain	0.034	T
BayesDel_noAF	Benign	-0.19
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.32	T
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Benign	0.75	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.055	D
MetaRNN	Uncertain	0.48	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		6.4
PrimateAI	Uncertain	0.70	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.28
Sift	Uncertain	0.018	D
Sift4G	Uncertain	0.027	D
Polyphen		1.0	D
Vest4		0.55
MutPred		0.55		Loss of MoRF binding (P = 0.0016)
MVP		0.27
MPC		2.6
ClinPred		0.99	D
GERP RS		3.4
PromoterAI		-0.037	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.44
gMVP		0.80
Mutation Taster		=55/45	polymorphism

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

Other links and lift over

dbSNP: rs1193797245; hg19: chr1-113933930; COSMIC: COSV56842720;