rs113328438

Positions:

• chr19-35295975-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.37

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 -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	UniProt
MAG	NM_002361.4	c.409A>G	p.Ile137Val	missense_variant	4/11	ENST00000392213.8
MAG	NM_001199216.2	c.334A>G	p.Ile112Val	missense_variant	4/11
MAG	NM_080600.3	c.409A>G	p.Ile137Val	missense_variant	4/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAG	ENST00000392213.8	c.409A>G	p.Ile137Val	missense_variant	4/11	1	NM_002361.4	P1

Frequencies

GnomAD3 genomes AF: 0.00995 AC: 1515 AN: 152194 Hom.: 37 Cov.: 32

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.: 10 AF XY: 0.00202 AC XY: 238 AN XY: 117936

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.: 20 Cov.: 32 AF XY: 0.000972 AC XY: 682 AN XY: 701790

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.: 38 Cov.: 32 AF XY: 0.00925 AC XY: 689 AN XY: 74486

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.: 9

Bravo AF: 0.0114

ESP6500AA AF: 0.0386 AC: 170

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00325 AC: 394

Asia WGS AF: 0.00635 AC: 22 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Hereditary spastic paraplegia 75 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 09, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	8.4
DANN	Benign	0.77
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.25
FATHMM_MKL	Benign	0.38	N
LIST_S2	Benign	0.67	T;T;T;T;T
MetaRNN	Benign	0.0027	T;T;T;T;T
MetaSVM	Benign	-0.96	T
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.52	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	T
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

Other links and lift over

dbSNP: rs113328438; hg19: chr19-35786878;