1-113622884-C-G

Variant names:

• chr1-113622884-C-G
• rs145442738
• NM_001142782.2:c.1250C>G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001142782.2(MAGI3):​c.1250C>G​(p.Thr417Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000551 in 1,451,428 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign 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. T417I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: MAGI3 NM_001142782.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.55

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 Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.21277061).
• BS2: High AC in GnomAdExome4 at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGI3	NM_001142782.2	c.1250C>G	p.Thr417Arg	missense_variant	Exon 9 of 21	ENST00000307546.14	NP_001136254.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAGI3	ENST00000307546.14	c.1250C>G	p.Thr417Arg	missense_variant	Exon 9 of 21	5	NM_001142782.2	ENSP00000304604.9
MAGI3	ENST00000369617.8	c.1325C>G	p.Thr442Arg	missense_variant	Exon 10 of 22	1		ENSP00000358630.4
MAGI3	ENST00000369611.4	c.1250C>G	p.Thr417Arg	missense_variant	Exon 9 of 21	1		ENSP00000358624.4
MAGI3	ENST00000369615.5	c.1250C>G	p.Thr417Arg	missense_variant	Exon 9 of 22	5		ENSP00000358628.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.00000413 AC: 1 AN: 242152 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 131262

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000902

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000551 AC: 8 AN: 1451428 Hom.: 0 Cov.: 30 AF XY: 0.00000416 AC XY: 3 AN XY: 721672

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: 0.00000722

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Uncertain	24
DANN	Benign	0.97
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.85	T;T;.;T
M_CAP	Benign	0.0069	T
MetaRNN	Benign	0.21	T;T;T;T
MetaSVM	Benign	-1.2	T
MutationAssessor	Benign	0.50	N;.;.;.
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-1.2	N;N;N;N
REVEL	Benign	0.077
Sift	Benign	0.34	T;T;T;T
Sift4G	Benign	0.58	T;T;T;T
Polyphen		0.14	B;.;P;P
Vest4		0.33
MVP		0.12
MPC		0.37
ClinPred		0.35	T
GERP RS		5.8
Varity_R		0.18
gMVP		0.51

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: rs145442738; hg19: chr1-114165506;