19-35300381-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002361.4(MAG):​c.947G>A​(p.Arg316His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000126 in 1,582,238 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R316L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

MAG
NM_002361.4 missense

Scores

4
15

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.03
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.1359047).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MAGNM_002361.4 linkuse as main transcriptc.947G>A p.Arg316His missense_variant 6/11 ENST00000392213.8
MAGNM_001199216.2 linkuse as main transcriptc.872G>A p.Arg291His missense_variant 6/11
MAGNM_080600.3 linkuse as main transcriptc.947G>A p.Arg316His missense_variant 6/12

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MAGENST00000392213.8 linkuse as main transcriptc.947G>A p.Arg316His missense_variant 6/111 NM_002361.4 P1P20916-1
MAGENST00000537831.2 linkuse as main transcriptc.872G>A p.Arg291His missense_variant 6/111 P20916-3
MAGENST00000361922.8 linkuse as main transcriptc.947G>A p.Arg316His missense_variant 6/121 P20916-2

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152206
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000438
AC:
1
AN:
228398
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
125136
show subpopulations
Gnomad AFR exome
AF:
0.0000650
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.99e-7
AC:
1
AN:
1430032
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
708554
show subpopulations
Gnomad4 AFR exome
AF:
0.0000301
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152206
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74360
show subpopulations
Gnomad4 AFR
AF:
0.0000241
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:
0.00
Gnomad4 OTH
AF:
0.00
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000165
AC:
2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.074
BayesDel_addAF
Benign
-0.015
T
BayesDel_noAF
Benign
-0.26
CADD
Benign
23
DANN
Uncertain
0.99
DEOGEN2
Benign
0.17
T;.;.
Eigen
Benign
-0.44
Eigen_PC
Benign
-0.31
FATHMM_MKL
Benign
0.59
D
LIST_S2
Benign
0.78
T;T;T
M_CAP
Uncertain
0.11
D
MetaRNN
Benign
0.14
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.4
L;L;.
MutationTaster
Benign
0.95
N;N;N
PrimateAI
Uncertain
0.61
T
PROVEAN
Uncertain
-2.4
N;N;N
REVEL
Benign
0.19
Sift
Benign
0.15
T;T;T
Sift4G
Benign
0.42
T;T;T
Polyphen
0.036
B;.;.
Vest4
0.30
MVP
0.57
MPC
0.55
ClinPred
0.13
T
GERP RS
2.5
Varity_R
0.15
gMVP
0.64

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.

Other links and lift over

dbSNP: rs370453303; hg19: chr19-35791284; API