rs17274634

Variant names:

• chr1-113674905-T-C
• rs17274634
• NM_001142782.2:c.3189+1440T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001142782.2(MAGI3):​c.3189+1440T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.24 in 152,090 control chromosomes in the GnomAD database, including 4,873 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.24 (4873 hom., cov: 32)
• Consequence: MAGI3 NM_001142782.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0860
• Publications: 9 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.374 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGI3	NM_001142782.2	c.3189+1440T>C		intron_variant	Intron 19 of 20	ENST00000307546.14	NP_001136254.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAGI3	ENST00000307546.14	c.3189+1440T>C		intron_variant	Intron 19 of 20	5	NM_001142782.2	ENSP00000304604.9
MAGI3	ENST00000369617.8	c.3264+1440T>C		intron_variant	Intron 20 of 21	1		ENSP00000358630.4
MAGI3	ENST00000369611.4	c.3189+1440T>C		intron_variant	Intron 19 of 20	1		ENSP00000358624.4
MAGI3	ENST00000369615.5	c.3189+1440T>C		intron_variant	Intron 19 of 21	5		ENSP00000358628.1

Frequencies

GnomAD3 genomes AF: 0.240 AC: 36461 AN: 151972 Hom.: 4872 Cov.: 32

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.292

Gnomad AMR AF: 0.240

Gnomad ASJ AF: 0.297

Gnomad EAS AF: 0.0909

Gnomad SAS AF: 0.389

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.297

Gnomad OTH AF: 0.257

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.240 AC: 36483 AN: 152090 Hom.: 4873 Cov.: 32 AF XY: 0.239 AC XY: 17793 AN XY: 74334

African (AFR) AF: 0.137 AC: 5686 AN: 41478

American (AMR) AF: 0.241 AC: 3682 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.297 AC: 1032 AN: 3470

East Asian (EAS) AF: 0.0909 AC: 470 AN: 5172

South Asian (SAS) AF: 0.389 AC: 1875 AN: 4822

European-Finnish (FIN) AF: 0.249 AC: 2631 AN: 10558

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.297 AC: 20202 AN: 67988

Other (OTH) AF: 0.257 AC: 543 AN: 2112

Alfa AF: 0.279 Hom.: 23609

Bravo AF: 0.232

Asia WGS AF: 0.239 AC: 833 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.1
DANN	Benign	0.63
PhyloP100		-0.086
Mutation Taster		=100/0	polymorphism (auto)

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: rs17274634; hg19: chr1-114217527;