NM_002361.4:c.47-4G>T

Variant names:

• chr19-35295609-G-T
• rs147119099
• NM_002361.4:c.47-4G>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_002361.4(MAG):​c.47-4G>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00854 in 1,598,704 control chromosomes in the GnomAD database, including 67 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0062 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0088 (63 hom.)
• Consequence: MAG NM_002361.4 splice_region, intron
• Scores: Splicing: ADA: 0.0005542
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.663
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• complex hereditary spastic paraplegia

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• hereditary spastic paraplegia 75

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 19-35295609-G-T is Benign according to our data. Variant chr19-35295609-G-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 252776.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00616 (938/152254) while in subpopulation NFE AF = 0.00943 (641/68008). AF 95% confidence interval is 0.00882. There are 4 homozygotes in GnomAd4. There are 411 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002361.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAG	NM_002361.4	MANE Select	c.47-4G>T		splice_region intron	N/A	NP_002352.1
	MAG	NM_001199216.2		c.-29-4G>T		splice_region intron	N/A	NP_001186145.1
	MAG	NM_080600.3		c.47-4G>T		splice_region intron	N/A	NP_542167.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAG	ENST00000392213.8	TSL:1 MANE Select	c.47-4G>T		splice_region intron	N/A	ENSP00000376048.2
	MAG	ENST00000537831.2	TSL:1	c.-29-4G>T		splice_region intron	N/A	ENSP00000440695.1
	MAG	ENST00000361922.8	TSL:1	c.47-4G>T		splice_region intron	N/A	ENSP00000355234.4

Frequencies

GnomAD3 genomes AF: 0.00618 AC: 940 AN: 152136 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.00191

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00648

Gnomad ASJ AF: 0.0205

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00254

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00942

Gnomad OTH AF: 0.00860

GnomAD2 exomes AF: 0.00610 AC: 1457 AN: 238742 AF XY: 0.00630

Gnomad AFR exome AF: 0.00161

Gnomad AMR exome AF: 0.00437

Gnomad ASJ exome AF: 0.0202

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00320

Gnomad NFE exome AF: 0.00900

Gnomad OTH exome AF: 0.00724

GnomAD4 exome AF: 0.00878 AC: 12707 AN: 1446450 Hom.: 63 Cov.: 31 AF XY: 0.00856 AC XY: 6146 AN XY: 718400

African (AFR) AF: 0.000989 AC: 33 AN: 33366

American (AMR) AF: 0.00470 AC: 207 AN: 44004

Ashkenazi Jewish (ASJ) AF: 0.0198 AC: 498 AN: 25160

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39608

South Asian (SAS) AF: 0.000878 AC: 74 AN: 84242

European-Finnish (FIN) AF: 0.00398 AC: 196 AN: 49288

Middle Eastern (MID) AF: 0.00769 AC: 41 AN: 5330

European-Non Finnish (NFE) AF: 0.0101 AC: 11176 AN: 1105598

Other (OTH) AF: 0.00804 AC: 481 AN: 59854

GnomAD4 genome AF: 0.00616 AC: 938 AN: 152254 Hom.: 4 Cov.: 32 AF XY: 0.00552 AC XY: 411 AN XY: 74442

African (AFR) AF: 0.00190 AC: 79 AN: 41546

American (AMR) AF: 0.00647 AC: 99 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0205 AC: 71 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00254 AC: 27 AN: 10614

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.00943 AC: 641 AN: 68008

Other (OTH) AF: 0.00803 AC: 17 AN: 2116

Alfa AF: 0.00598 Hom.: 1

Bravo AF: 0.00657

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Oct 30, 2015

Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Aug 18, 2025

Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided Benign:2

Aug 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

MAG: BP4, BS1, BS2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Hereditary spastic paraplegia 75 Benign:1

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.48
DANN	Benign	0.77
PhyloP100		-0.66
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00055
dbscSNV1_RF	Benign	0.022
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs147119099; hg19: chr19-35786512;