Genetic Variant MAG:p.Ser133Ser (chr19-35295965-C-T) – ACMG Classification: Benign (-19 pts)

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_002361.4(MAG):c.399C>T(p.Ser133Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.239 in 1,590,544 control chromosomes in the GnomAD database, including 48,238 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 3910 hom., cov: 32)

Exomes 𝑓: 0.24 ( 44328 hom. )

Consequence

MAG
NM_002361.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.368

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BP6

Variant 19-35295965-C-T is Benign according to our data. Variant chr19-35295965-C-T is described in ClinVar as [Benign]. Clinvar id is 1168325.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.368 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.398 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAG	NM_002361.4 link	c.399C>T	p.Ser133Ser	synonymous_variant	Exon 4 of 11	ENST00000392213.8	NP_002352.1	P20916-1Q53ES7
MAG	NM_001199216.2 link	c.324C>T	p.Ser108Ser	synonymous_variant	Exon 4 of 11		NP_001186145.1	P20916-3
MAG	NM_080600.3 link	c.399C>T	p.Ser133Ser	synonymous_variant	Exon 4 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.399C>T	p.Ser133Ser	synonymous_variant	Exon 4 of 11	1	NM_002361.4	ENSP00000376048.2		P20916-1

Frequencies

GnomAD3 genomes

AF:

0.213

AC:

32357

AN:

152038

Hom.:

3901

Cov.:

show subpopulations

Gnomad AFR

AF:

0.123

Gnomad AMI

AF:

0.188

Gnomad AMR

AF:

0.307

Gnomad ASJ

AF:

0.227

Gnomad EAS

AF:

0.413

Gnomad SAS

AF:

0.362

Gnomad FIN

AF:

0.220

Gnomad MID

AF:

0.193

Gnomad NFE

AF:

0.219

Gnomad OTH

AF:

0.210

GnomAD3 exomes

AF:

0.274

AC:

63903

AN:

233174

Hom.:

9719

AF XY:

0.274

AC XY:

34641

AN XY:

126328

show subpopulations

Gnomad AFR exome

AF:

0.121

Gnomad AMR exome

AF:

0.391

Gnomad ASJ exome

AF:

0.242

Gnomad EAS exome

AF:

0.410

Gnomad SAS exome

AF:

0.366

Gnomad FIN exome

AF:

0.223

Gnomad NFE exome

AF:

0.227

Gnomad OTH exome

AF:

0.265

GnomAD4 exome

AF:

0.242

AC:

347399

AN:

1438388

Hom.:

44328

Cov.:

AF XY:

0.245

AC XY:

174693

AN XY:

712896

show subpopulations

Gnomad4 AFR exome

AF:

0.120

Gnomad4 AMR exome

AF:

0.381

Gnomad4 ASJ exome

AF:

0.228

Gnomad4 EAS exome

AF:

0.422

Gnomad4 SAS exome

AF:

0.356

Gnomad4 FIN exome

AF:

0.219

Gnomad4 NFE exome

AF:

0.226

Gnomad4 OTH exome

AF:

0.247

GnomAD4 genome

AF:

0.213

AC:

32398

AN:

152156

Hom.:

3910

Cov.:

AF XY:

0.219

AC XY:

16286

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.123

Gnomad4 AMR

AF:

0.308

Gnomad4 ASJ

AF:

0.227

Gnomad4 EAS

AF:

0.413

Gnomad4 SAS

AF:

0.363

Gnomad4 FIN

AF:

0.220

Gnomad4 NFE

AF:

0.219

Gnomad4 OTH

AF:

0.211

Alfa

AF:

0.223

Hom.:

6020

Bravo

AF:

0.213

Asia WGS

AF:

0.373

AC:

1300

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Hereditary spastic paraplegia 75

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Sep 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Benign

0.89

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