chr19-35295596-C-G

Variant names:

• chr19-35295596-C-G
• rs201985530
• NM_002361.4:c.47-17C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002361.4(MAG):​c.47-17C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000415 in 1,444,122 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000042 (0 hom.)
• Consequence: MAG NM_002361.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.641
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAG	NM_002361.4	MANE Select	c.47-17C>G		intron	N/A	NP_002352.1	P20916-1
	MAG	NM_001199216.2		c.-29-17C>G		intron	N/A	NP_001186145.1	P20916-3
	MAG	NM_080600.3		c.47-17C>G		intron	N/A	NP_542167.1	P20916-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAG	ENST00000392213.8	TSL:1 MANE Select	c.47-17C>G		intron	N/A	ENSP00000376048.2	P20916-1
	MAG	ENST00000537831.2	TSL:1	c.-29-17C>G		intron	N/A	ENSP00000440695.1	P20916-3
	MAG	ENST00000361922.8	TSL:1	c.47-17C>G		intron	N/A	ENSP00000355234.4	P20916-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000423 AC: 1 AN: 236474 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000926

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000415 AC: 6 AN: 1444122 Hom.: 0 Cov.: 31 AF XY: 0.00000558 AC XY: 4 AN XY: 716938

African (AFR) AF: 0.00 AC: 0 AN: 33352

American (AMR) AF: 0.00 AC: 0 AN: 43930

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24920

East Asian (EAS) AF: 0.00 AC: 0 AN: 39614

South Asian (SAS) AF: 0.00 AC: 0 AN: 83464

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49590

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5124

European-Non Finnish (NFE) AF: 0.00000543 AC: 6 AN: 1104404

Other (OTH) AF: 0.00 AC: 0 AN: 59724

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	3.6
DANN	Benign	0.60
PhyloP100		0.64

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

Other links and lift over

dbSNP: rs201985530; hg19: chr19-35786499;