NM_012301.4:c.98A>T

Variant names:

• chr7-79453223-T-A
• rs895041574
• NM_012301.4:c.98A>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_012301.4(MAGI2):​c.98A>T​(p.Lys33Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MAGI2 NM_012301.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.77
• Publications: 0 publications found

Genes affected

MAGI2 (HGNC:18957): (membrane associated guanylate kinase, WW and PDZ domain containing 2) The protein encoded by this gene interacts with atrophin-1. Atrophin-1 contains a polyglutamine repeat, expansion of which is responsible for dentatorubral and pallidoluysian atrophy. This encoded protein is characterized by two WW domains, a guanylate kinase-like domain, and multiple PDZ domains. It has structural similarity to the membrane-associated guanylate kinase homologue (MAGUK) family. [provided by RefSeq, Jul 2008]

MAGI2-AS3 (HGNC:40862): (MAGI2 antisense RNA 3)

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37776798).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012301.4. 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
	MAGI2	NM_012301.4	MANE Select	c.98A>T	p.Lys33Met	missense	Exon 1 of 22	NP_036433.2
	MAGI2	NM_001301128.2		c.98A>T	p.Lys33Met	missense	Exon 1 of 21	NP_001288057.1	Q86UL8-2
	MAGI2-AS3	NR_038345.1		n.235+32T>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAGI2	ENST00000354212.9	TSL:1 MANE Select	c.98A>T	p.Lys33Met	missense	Exon 1 of 22	ENSP00000346151.4	Q86UL8-1
	MAGI2	ENST00000419488.5	TSL:1	c.98A>T	p.Lys33Met	missense	Exon 1 of 21	ENSP00000405766.1	Q86UL8-2
	MAGI2	ENST00000522391.3	TSL:5	c.98A>T	p.Lys33Met	missense	Exon 1 of 23	ENSP00000428389.1	E7EWI0

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Nephrotic syndrome 15 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.43	T
Eigen	Uncertain	0.22
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.38	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
PhyloP100		1.8
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-0.70	N
REVEL	Benign	0.15
Sift	Benign	0.040	D
Sift4G	Uncertain	0.039	D
Polyphen		0.81	P
Vest4		0.53
MutPred		0.57		Loss of ubiquitination at K33 (P = 0.0071)
MVP		0.19
MPC		2.1
ClinPred		0.84	D
GERP RS		2.8
PromoterAI		-0.013	Neutral
Varity_R		0.11
gMVP		0.76
Mutation Taster		=74/26	polymorphism

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: rs895041574; hg19: chr7-79082539;