rs35855737

Variant names:

• chr3-65557181-T-C
• rs35855737
• NM_001033057.2:c.431-63550A>G

Variant summary

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

The NM_001033057.2(MAGI1):​c.431-63550A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 152,272 control chromosomes in the GnomAD database, including 1,617 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 0.13 (1617 hom., cov: 33)
• Consequence: MAGI1 NM_001033057.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.02
• Publications: 16 publications found

Genes affected

MAGI1 (HGNC:946): (membrane associated guanylate kinase, WW and PDZ domain containing 1) The protein encoded by this gene is a member of the membrane-associated guanylate kinase homologue (MAGUK) family. MAGUK proteins participate in the assembly of multiprotein complexes on the inner surface of the plasma membrane at regions of cell-cell contact. The product of this gene may play a role as scaffolding protein at cell-cell junctions. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.187 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001033057.2. 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
	MAGI1	NM_001033057.2	MANE Select	c.431-63550A>G		intron	N/A	NP_001028229.1	Q96QZ7-2
	MAGI1	NM_001365903.2		c.431-63550A>G		intron	N/A	NP_001352832.1
	MAGI1	NM_001365904.2		c.431-63550A>G		intron	N/A	NP_001352833.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAGI1	ENST00000402939.7	TSL:1 MANE Select	c.431-63550A>G		intron	N/A	ENSP00000385450.2	Q96QZ7-2
	MAGI1	ENST00000330909.12	TSL:1	c.431-63550A>G		intron	N/A	ENSP00000331157.7	Q96QZ7-5
	MAGI1	ENST00000483466.5	TSL:1	c.431-63550A>G		intron	N/A	ENSP00000420323.1	Q96QZ7-3

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19296 AN: 152154 Hom.: 1618 Cov.: 33

Gnomad AFR AF: 0.0332

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.117

Gnomad ASJ AF: 0.252

Gnomad EAS AF: 0.000963

Gnomad SAS AF: 0.0708

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.189

Gnomad OTH AF: 0.135

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

GnomAD4 genome AF: 0.127 AC: 19289 AN: 152272 Hom.: 1617 Cov.: 33 AF XY: 0.125 AC XY: 9286 AN XY: 74442

African (AFR) AF: 0.0331 AC: 1376 AN: 41568

American (AMR) AF: 0.117 AC: 1783 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.252 AC: 873 AN: 3470

East Asian (EAS) AF: 0.000965 AC: 5 AN: 5180

South Asian (SAS) AF: 0.0708 AC: 342 AN: 4828

European-Finnish (FIN) AF: 0.151 AC: 1601 AN: 10606

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.189 AC: 12877 AN: 68000

Other (OTH) AF: 0.134 AC: 283 AN: 2114

Alfa AF: 0.108 Hom.: 488

Bravo AF: 0.119

Asia WGS AF: 0.0280 AC: 97 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.024
DANN	Benign	0.62
PhyloP100		-3.0
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: rs35855737; hg19: chr3-65542856;