19-35302474-G-C

Position:

• chr19-35302474-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_002361.4(MAG):​c.997G>C​(p.Gly333Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: MAG NM_002361.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.11

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37704948).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAG	NM_002361.4	c.997G>C	p.Gly333Arg	missense_variant	7/11	ENST00000392213.8	NP_002352.1
MAG	NM_001199216.2	c.922G>C	p.Gly308Arg	missense_variant	7/11		NP_001186145.1
MAG	NM_080600.3	c.997G>C	p.Gly333Arg	missense_variant	7/12		NP_542167.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAG	ENST00000392213.8	c.997G>C	p.Gly333Arg	missense_variant	7/11	1	NM_002361.4	ENSP00000376048.2
MAG	ENST00000537831.2	c.922G>C	p.Gly308Arg	missense_variant	7/11	1		ENSP00000440695.1
MAG	ENST00000361922.8	c.997G>C	p.Gly333Arg	missense_variant	7/12	1		ENSP00000355234.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461874 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 727238

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Benign	22
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.093	T;.;.
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.78	T;T;T
M_CAP	Benign	0.074	D
MetaRNN	Benign	0.38	T;T;T
MetaSVM	Benign	-0.69	T
MutationAssessor	Benign	0.96	L;L;.
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-1.1	N;N;N
REVEL	Benign	0.26
Sift	Uncertain	0.013	D;T;D
Sift4G	Benign	0.082	T;T;T
Polyphen		1.0	D;.;.
Vest4		0.37
MutPred		0.41		Loss of ubiquitination at K328 (P = 0.0557);Loss of ubiquitination at K328 (P = 0.0557);.;
MVP		0.50
MPC		1.4
ClinPred		0.96	D
GERP RS		5.3
Varity_R		0.16
gMVP		0.71

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: rs199764089; hg19: chr19-35793377;