19-35295965-C-G

Variant names:

• chr19-35295965-C-G
• rs2301600
• NM_002361.4:c.399C>G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP5

The NM_002361.4(MAG):​c.399C>G​(p.Ser133Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MAG NM_002361.4 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 0.368

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 19-35295965-C-G is Pathogenic according to our data. Variant chr19-35295965-C-G is described in ClinVar as [Pathogenic]. Clinvar id is 218187.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAG	NM_002361.4	c.399C>G	p.Ser133Arg	missense_variant	Exon 4 of 11	ENST00000392213.8	NP_002352.1
MAG	NM_001199216.2	c.324C>G	p.Ser108Arg	missense_variant	Exon 4 of 11		NP_001186145.1
MAG	NM_080600.3	c.399C>G	p.Ser133Arg	missense_variant	Exon 4 of 12		NP_542167.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAG	ENST00000392213.8	c.399C>G	p.Ser133Arg	missense_variant	Exon 4 of 11	1	NM_002361.4	ENSP00000376048.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Hereditary spastic paraplegia 75 Pathogenic:1

Sep 01, 2015

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Benign	-0.021	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	.;T;.;.;.
Eigen	Benign	-0.038
Eigen_PC	Benign	-0.016
FATHMM_MKL	Benign	0.56	D
LIST_S2	Benign	0.85	T;T;T;T;T
M_CAP	Benign	0.037	D
MetaRNN	Uncertain	0.45	T;T;T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.0	.;N;N;.;.
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-0.88	.;N;N;.;N
REVEL	Benign	0.22
Sift	Benign	0.11	.;T;T;.;D
Sift4G	Benign	0.12	T;T;T;T;T
Polyphen		0.99	.;D;.;.;.
Vest4		0.65, 0.66, 0.63
MutPred		0.52		.;Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);.;
MVP		0.74
MPC		0.62
ClinPred		0.45	T
GERP RS		2.8
Varity_R		0.13
gMVP		0.78

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: rs2301600; hg19: chr19-35786868;