rs770946769

Variant names:

• chr19-35299619-G-C
• rs770946769
• NM_002361.4:c.481G>C

Your query was ambiguous. Multiple possible variants found:

• chr19-35299619-G-C
• chr19-35299619-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_002361.4(MAG):​c.481G>C​(p.Val161Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 25)
• Consequence: MAG NM_002361.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.80
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.481G>C	p.Val161Leu	missense	Exon 5 of 11	NP_002352.1	P20916-1
	MAG	NM_001199216.2		c.406G>C	p.Val136Leu	missense	Exon 5 of 11	NP_001186145.1	P20916-3
	MAG	NM_080600.3		c.481G>C	p.Val161Leu	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.481G>C	p.Val161Leu	missense	Exon 5 of 11	ENSP00000376048.2	P20916-1
	MAG	ENST00000537831.2	TSL:1	c.406G>C	p.Val136Leu	missense	Exon 5 of 11	ENSP00000440695.1	P20916-3
	MAG	ENST00000361922.8	TSL:1	c.481G>C	p.Val161Leu	missense	Exon 5 of 12	ENSP00000355234.4	P20916-2

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 25

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Hereditary spastic paraplegia 75 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.52
BayesDel_addAF	Uncertain	0.067	T
BayesDel_noAF	Benign	-0.14
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.24	T
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.87	D
M_CAP	Pathogenic	0.44	D
MetaRNN	Uncertain	0.51	D
MetaSVM	Uncertain	-0.13	T
MutationAssessor	Benign	1.9	L
PhyloP100		6.8
PrimateAI	Pathogenic	0.79	T
PROVEAN	Benign	-0.33	N
REVEL	Uncertain	0.45
Sift	Benign	0.091	T
Sift4G	Uncertain	0.030	D
Polyphen		0.97	D
Vest4		0.50
MutPred		0.61		Loss of glycosylation at S158 (P = 0.091)
MVP		0.75
MPC		1.1
ClinPred		0.96	D
GERP RS		4.6
Varity_R		0.25
gMVP		0.80
Mutation Taster		=56/44	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: rs770946769; hg19: chr19-35790522;