1-113590628-A-C

Variant names:

• chr1-113590628-A-C
• NM_001142782.2:c.908A>C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001142782.2(MAGI3):​c.908A>C​(p.Tyr303Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,538 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y303C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: MAGI3 NM_001142782.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.91

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.858

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGI3	NM_001142782.2	c.908A>C	p.Tyr303Ser	missense_variant	Exon 5 of 21	ENST00000307546.14	NP_001136254.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAGI3	ENST00000307546.14	c.908A>C	p.Tyr303Ser	missense_variant	Exon 5 of 21	5	NM_001142782.2	ENSP00000304604.9
MAGI3	ENST00000369617.8	c.908A>C	p.Tyr303Ser	missense_variant	Exon 5 of 22	1		ENSP00000358630.4
MAGI3	ENST00000369611.4	c.908A>C	p.Tyr303Ser	missense_variant	Exon 5 of 21	1		ENSP00000358624.4
MAGI3	ENST00000369615.5	c.908A>C	p.Tyr303Ser	missense_variant	Exon 5 of 22	5		ENSP00000358628.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461538 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727070

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.91
BayesDel_addAF	Pathogenic	0.39	D
BayesDel_noAF	Pathogenic	0.33
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Pathogenic	0.85	.;D;.;.
Eigen	Pathogenic	0.79
Eigen_PC	Pathogenic	0.77
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D;D;.;D
M_CAP	Uncertain	0.22	D
MetaRNN	Pathogenic	0.86	D;D;D;D
MetaSVM	Uncertain	0.31	D
MutationAssessor	Benign	1.6	L;L;L;L
PrimateAI	Pathogenic	0.80	T
PROVEAN	Pathogenic	-7.1	D;D;D;D
REVEL	Pathogenic	0.93
Sift	Uncertain	0.027	D;D;D;D
Sift4G	Uncertain	0.0020	D;D;D;D
Polyphen		1.0	D;.;D;D
Vest4		0.81
MutPred		0.55		Gain of disorder (P = 0.0283);Gain of disorder (P = 0.0283);Gain of disorder (P = 0.0283);Gain of disorder (P = 0.0283);
MVP		0.77
MPC		0.79
ClinPred		1.0	D
GERP RS		5.7
Varity_R		0.85
gMVP		0.71

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: chr1-114133250;