19-35309930-T-G

Position:

• chr19-35309930-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2 PP3_Moderate PP5

The NM_002361.4(MAG):​c.1288T>G​(p.Cys430Gly) variant causes a missense change. 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 Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: MAG NM_002361.4 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 5.37

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.899
• PP5: Variant 19-35309930-T-G is Pathogenic according to our data. Variant chr19-35309930-T-G is described in ClinVar as [Pathogenic]. Clinvar id is 120188.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAG	NM_002361.4	c.1288T>G	p.Cys430Gly	missense_variant	8/11	ENST00000392213.8	NP_002352.1
MAG	NM_001199216.2	c.1213T>G	p.Cys405Gly	missense_variant	8/11		NP_001186145.1
MAG	NM_080600.3	c.1288T>G	p.Cys430Gly	missense_variant	8/12		NP_542167.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAG	ENST00000392213.8	c.1288T>G	p.Cys430Gly	missense_variant	8/11	1	NM_002361.4	ENSP00000376048.2
MAG	ENST00000537831.2	c.1213T>G	p.Cys405Gly	missense_variant	8/11	1		ENSP00000440695.1
MAG	ENST00000361922.8	c.1288T>G	p.Cys430Gly	missense_variant	8/12	1		ENSP00000355234.4
MAG	ENST00000593348.1	n.125T>G		non_coding_transcript_exon_variant	1/3	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Hereditary spastic paraplegia 75 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jan 31, 2014

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
CADD	Pathogenic	29
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.59	D;.;.
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.79	T;T;T
M_CAP	Uncertain	0.16	D
MetaRNN	Pathogenic	0.90	D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L;L;.
PrimateAI	Uncertain	0.71	T
PROVEAN	Pathogenic	-9.8	D;D;D
REVEL	Pathogenic	0.78
Sift	Pathogenic	0.0	D;D;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		1.0	D;.;.
Vest4		0.91
MutPred		0.63		Loss of stability (P = 0.0591);Loss of stability (P = 0.0591);.;
MVP		0.72
MPC		1.2
ClinPred		1.0	D
GERP RS		4.8
Varity_R		0.96
gMVP		0.98

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

Publications

LitVar

Other links and lift over

dbSNP: rs587777229; hg19: chr19-35800833;