rs3746248

chr19-35299600-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_002361.4(MAG):c.462G>A(p.Glu154=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 1,605,214 control chromosomes in the GnomAD database, including 53,956 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.35 (12254 hom., cov: 26)
  • Exomes 𝑓: 0.22 (41702 hom.)
• Consequence: MAG NM_002361.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.0520

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 Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 19-35299600-G-A is Benign according to our data. Variant chr19-35299600-G-A is described in ClinVar as [Benign]. Clinvar id is 1168416.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.052 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.668 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAG	NM_002361.4	c.462G>A	p.Glu154=	synonymous_variant	5/11	ENST00000392213.8
MAG	NM_001199216.2	c.387G>A	p.Glu129=	synonymous_variant	5/11
MAG	NM_080600.3	c.462G>A	p.Glu154=	synonymous_variant	5/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAG	ENST00000392213.8	c.462G>A	p.Glu154=	synonymous_variant	5/11	1	NM_002361.4	P1

Frequencies

GnomAD3 genomes AF: 0.346 AC: 52391 AN: 151296 Hom.: 12231 Cov.: 26

Gnomad AFR AF: 0.675

Gnomad AMI AF: 0.225

Gnomad AMR AF: 0.252

Gnomad ASJ AF: 0.249

Gnomad EAS AF: 0.361

Gnomad SAS AF: 0.257

Gnomad FIN AF: 0.199

Gnomad MID AF: 0.290

Gnomad NFE AF: 0.204

Gnomad OTH AF: 0.319

GnomAD3 exomes AF: 0.258 AC: 62980 AN: 244250 Hom.: 9863 AF XY: 0.250 AC XY: 33194 AN XY: 132608

Gnomad AFR exome AF: 0.680

Gnomad AMR exome AF: 0.203

Gnomad ASJ exome AF: 0.263

Gnomad EAS exome AF: 0.361

Gnomad SAS exome AF: 0.251

Gnomad FIN exome AF: 0.206

Gnomad NFE exome AF: 0.209

Gnomad OTH exome AF: 0.235

GnomAD4 exome AF: 0.225 AC: 326661 AN: 1453800 Hom.: 41702 Cov.: 35 AF XY: 0.224 AC XY: 161564 AN XY: 721642

Gnomad4 AFR exome AF: 0.686

Gnomad4 AMR exome AF: 0.208

Gnomad4 ASJ exome AF: 0.257

Gnomad4 EAS exome AF: 0.379

Gnomad4 SAS exome AF: 0.248

Gnomad4 FIN exome AF: 0.201

Gnomad4 NFE exome AF: 0.203

Gnomad4 OTH exome AF: 0.252

GnomAD4 genome AF: 0.347 AC: 52467 AN: 151414 Hom.: 12254 Cov.: 26 AF XY: 0.344 AC XY: 25421 AN XY: 73954

Gnomad4 AFR AF: 0.674

Gnomad4 AMR AF: 0.252

Gnomad4 ASJ AF: 0.249

Gnomad4 EAS AF: 0.361

Gnomad4 SAS AF: 0.257

Gnomad4 FIN AF: 0.199

Gnomad4 NFE AF: 0.204

Gnomad4 OTH AF: 0.321

Alfa AF: 0.236 Hom.: 8899

Bravo AF: 0.366

Asia WGS AF: 0.358 AC: 1246 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Hereditary spastic paraplegia 75 Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Sep 05, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 30, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	7.7
Dann	Benign	0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs3746248; hg19: chr19-35790503; COSMIC: COSV62703460;