3-65356704-G-A

Variant names:

• chr3-65356704-G-A
• NM_001033057.2:c.4063C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP6

The NM_001033057.2(MAGI1):​c.4063C>T​(p.Arg1355*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MAGI1 NM_001033057.2 stop_gained
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.62
• Publications: 0 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 3-65356704-G-A is Benign according to our data. Variant chr3-65356704-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2681384.Status of the report is no_assertion_criteria_provided, 0 stars.

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.4063C>T	p.Arg1355*	stop_gained	Exon 23 of 23	NP_001028229.1	Q96QZ7-2
	MAGI1	NM_001365903.2		c.*372C>T		3_prime_UTR	Exon 25 of 25	NP_001352832.1
	MAGI1	NM_001365904.2		c.*372C>T		3_prime_UTR	Exon 25 of 25	NP_001352833.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAGI1	ENST00000402939.7	TSL:1 MANE Select	c.4063C>T	p.Arg1355*	stop_gained	Exon 23 of 23	ENSP00000385450.2	Q96QZ7-2
	MAGI1	ENST00000621418.4	TSL:1	c.3142C>T	p.Arg1048*	stop_gained	Exon 22 of 22	ENSP00000477591.1	A0A087WT53
	MAGI1	ENST00000330909.12	TSL:1	c.*372C>T		3_prime_UTR	Exon 25 of 25	ENSP00000331157.7	Q96QZ7-5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	EBV-positive nodal T- and NK-cell lymphoma (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.45	D
BayesDel_noAF	Pathogenic	0.40
CADD	Pathogenic	37
DANN	Uncertain	1.0
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.84	D
PhyloP100		1.6
Vest4		0.65
GERP RS		3.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Mutation Taster		=34/166	disease causing

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr3-65342379; COSMIC: COSV100443540; COSMIC: COSV100443540;