NM_002361.4:c.462G>C

Variant names:

• chr19-35299600-G-C
• NM_002361.4:c.462G>C
• MAG p.Glu154Asp

Variant summary

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

The NM_002361.4(MAG):​c.462G>C​(p.Glu154Asp) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. E154E) has been classified as Benign.

• Frequency: Genomes: not found (cov: 26)
• Consequence: MAG NM_002361.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0520
• Publications: 0 publications found

Genes affected

MAG (HGNC:6783): (myelin associated glycoprotein) The protein encoded by this gene is a type I membrane protein and member of the immunoglobulin superfamily. It is thought to be involved in the process of myelination. It is a lectin that binds to sialylated glycoconjugates and mediates certain myelin-neuron cell-cell interactions. Three alternatively spliced transcripts encoding different isoforms have been described for this gene. [provided by RefSeq, Nov 2010]

MAG Gene-Disease associations (from GenCC):

• complex hereditary spastic paraplegia

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• hereditary spastic paraplegia 75

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

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=0.29271942).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002361.4. 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
	MAG	NM_002361.4	MANE Select	c.462G>C	p.Glu154Asp	missense	Exon 5 of 11	NP_002352.1	P20916-1
	MAG	NM_001199216.2		c.387G>C	p.Glu129Asp	missense	Exon 5 of 11	NP_001186145.1	P20916-3
	MAG	NM_080600.3		c.462G>C	p.Glu154Asp	missense	Exon 5 of 12	NP_542167.1	P20916-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAG	ENST00000392213.8	TSL:1 MANE Select	c.462G>C	p.Glu154Asp	missense	Exon 5 of 11	ENSP00000376048.2	P20916-1
	MAG	ENST00000537831.2	TSL:1	c.387G>C	p.Glu129Asp	missense	Exon 5 of 11	ENSP00000440695.1	P20916-3
	MAG	ENST00000361922.8	TSL:1	c.462G>C	p.Glu154Asp	missense	Exon 5 of 12	ENSP00000355234.4	P20916-2

Frequencies

GnomAD3 genomes Cov.: 26

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 26

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.0092	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.54	D
LIST_S2	Benign	0.80	T
M_CAP	Pathogenic	0.32	D
MetaRNN	Benign	0.29	T
MetaSVM	Uncertain	-0.27	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		-0.052
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-0.80	N
REVEL	Uncertain	0.37
Sift	Benign	0.15	T
Sift4G	Pathogenic	0.0	D
Varity_R		0.19
gMVP		0.48
Mutation Taster		=88/12	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr19-35790503;