rs113328438

Positions:

chr19-35295975-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_002361.4(MAG):c.409A>G(p.Ile137Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00196 in 1,573,478 control chromosomes in the GnomAD database, including 58 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.010 ( 38 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 20 hom. )

Consequence

MAG
NM_002361.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 1.37

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 Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002742052).

BP6

Variant 19-35295975-A-G is Benign according to our data. Variant chr19-35295975-A-G is described in ClinVar as [Benign]. Clinvar id is 542302.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.01 (1528/152312) while in subpopulation AFR AF= 0.0346 (1437/41568). AF 95% confidence interval is 0.0331. There are 38 homozygotes in gnomad4. There are 689 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 38 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MAG	NM_002361.4 linkuse as main transcript	c.409A>G	p.Ile137Val	missense_variant	4/11	ENST00000392213.8	NP_002352.1
MAG	NM_001199216.2 linkuse as main transcript	c.334A>G	p.Ile112Val	missense_variant	4/11		NP_001186145.1
MAG	NM_080600.3 linkuse as main transcript	c.409A>G	p.Ile137Val	missense_variant	4/12		NP_542167.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAG	ENST00000392213.8 linkuse as main transcript	c.409A>G	p.Ile137Val	missense_variant	4/11	1	NM_002361.4	ENSP00000376048	P1	P20916-1

Frequencies

GnomAD3 genomes

AF:

0.00995

AC:

1515

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0343

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00432

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00527

GnomAD3 exomes

AF:

0.00286

AC:

625

AN:

218356

Hom.:

AF XY:

0.00202

AC XY:

238

AN XY:

117936

show subpopulations

Gnomad AFR exome

AF:

0.0346

Gnomad AMR exome

AF:

0.00192

Gnomad ASJ exome

AF:

0.000140

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000207

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000219

Gnomad OTH exome

AF:

0.00175

GnomAD4 exome

AF:

0.00109

AC:

1556

AN:

1421166

Hom.:

Cov.:

AF XY:

0.000972

AC XY:

682

AN XY:

701790

show subpopulations

Gnomad4 AFR exome

AF:

0.0353

Gnomad4 AMR exome

AF:

0.00183

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000136

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000130

Gnomad4 OTH exome

AF:

0.00280

GnomAD4 genome

AF:

0.0100

AC:

1528

AN:

152312

Hom.:

Cov.:

AF XY:

0.00925

AC XY:

689

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.0346

Gnomad4 AMR

AF:

0.00431

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00521

Alfa

AF:

0.00193

Hom.:

Bravo

AF:

0.0114

ESP6500AA

AF:

0.0386

AC:

170

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00325

AC:

394

Asia WGS

AF:

0.00635

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Hereditary spastic paraplegia 75

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 09, 2024

- -

MAG-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 02, 2024

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.63

CADD

Benign

8.4

DANN

Benign

0.77

DEOGEN2

Benign

0.061

.;T;.;.;.

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.25

FATHMM_MKL

Benign

0.38

LIST_S2

Benign

0.67

T;T;T;T;T

MetaRNN

Benign

0.0027

T;T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-0.73

.;N;N;.;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-0.35

.;N;N;.;N

REVEL

Benign

0.066

Sift

Benign

1.0

.;T;T;.;T

Sift4G

Benign

1.0

T;T;T;T;T

Polyphen

0.010

.;B;.;.;.

Vest4

0.11, 0.11, 0.12

MVP

0.32

MPC

0.36

ClinPred

0.00084

GERP RS

4.2

Varity_R

0.029

gMVP

0.37

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over