Genetic Variant MAG:p.Val161Leu (chr19-35299619-G-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_002361.4(MAG):c.481G>T(p.Val161Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000372 in 1,610,814 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 25)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

MAG
NM_002361.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.80

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAG	NM_002361.4 link	c.481G>T	p.Val161Leu	missense_variant	Exon 5 of 11	ENST00000392213.8	NP_002352.1	P20916-1Q53ES7
MAG	NM_001199216.2 link	c.406G>T	p.Val136Leu	missense_variant	Exon 5 of 11		NP_001186145.1	P20916-3
MAG	NM_080600.3 link	c.481G>T	p.Val161Leu	missense_variant	Exon 5 of 12		NP_542167.1	P20916-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAG	ENST00000392213.8 link	c.481G>T	p.Val161Leu	missense_variant	Exon 5 of 11	1	NM_002361.4	ENSP00000376048.2		P20916-1

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151898

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000819

AC:

AN:

244142

Hom.:

AF XY:

0.0000151

AC XY:

AN XY:

132704

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000183

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1458916

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

725306

show subpopulations

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:

0.00000360

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151898

Hom.:

Cov.:

AF XY:

0.0000270

AC XY:

AN XY:

74172

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000565

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.52

BayesDel_addAF

Uncertain

0.067

BayesDel_noAF

Benign

-0.14

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.24

T;.;.

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.87

D;D;D

M_CAP

Pathogenic

0.44

MetaRNN

Uncertain

0.50

T;T;T

MetaSVM

Uncertain

-0.13

MutationAssessor

Benign

1.9

L;L;.

PrimateAI

Pathogenic

0.79

PROVEAN

Benign

-0.33

N;N;N

REVEL

Uncertain

0.45

Sift

Benign

0.091

T;T;T

Sift4G

Uncertain

0.030

D;D;D

Polyphen

0.97

D;.;.

Vest4

0.50

MutPred

0.61

Loss of glycosylation at S158 (P = 0.091);Loss of glycosylation at S158 (P = 0.091);.;

MVP

0.75

MPC

1.1

ClinPred

0.87

GERP RS

4.6

Varity_R

0.25

gMVP

0.80

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over