NM_001142782.2:c.704C>G

Variant names:

• chr1-113585537-C-G
• rs1648312472
• NM_001142782.2:c.704C>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001142782.2(MAGI3):​c.704C>G​(p.Ser235Cys) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MAGI3 NM_001142782.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.92

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3220011).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGI3	NM_001142782.2	c.704C>G	p.Ser235Cys	missense_variant	Exon 4 of 21	ENST00000307546.14	NP_001136254.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAGI3	ENST00000307546.14	c.704C>G	p.Ser235Cys	missense_variant	Exon 4 of 21	5	NM_001142782.2	ENSP00000304604.9
MAGI3	ENST00000369617.8	c.704C>G	p.Ser235Cys	missense_variant	Exon 4 of 22	1		ENSP00000358630.4
MAGI3	ENST00000369611.4	c.704C>G	p.Ser235Cys	missense_variant	Exon 4 of 21	1		ENSP00000358624.4
MAGI3	ENST00000369615.5	c.704C>G	p.Ser235Cys	missense_variant	Exon 4 of 22	5		ENSP00000358628.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 07, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.704C>G (p.S235C) alteration is located in exon 4 (coding exon 4) of the MAGI3 gene. This alteration results from a C to G substitution at nucleotide position 704, causing the serine (S) at amino acid position 235 to be replaced by a cysteine (C). 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
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.073	.;T;.;.
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.97	D;D;.;D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.32	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L;L;L;L
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.32	N;N;N;N
REVEL	Benign	0.23
Sift	Benign	0.053	T;T;D;D
Sift4G	Uncertain	0.052	T;T;T;T
Polyphen		0.99	D;.;D;D
Vest4		0.46
MutPred		0.47		Loss of phosphorylation at S235 (P = 0.0023);Loss of phosphorylation at S235 (P = 0.0023);Loss of phosphorylation at S235 (P = 0.0023);Loss of phosphorylation at S235 (P = 0.0023);
MVP		0.10
MPC		0.64
ClinPred		0.72	D
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.099
gMVP		0.39

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: rs1648312472; hg19: chr1-114128159;