19-35309966-G-T

Variant names:

• chr19-35309966-G-T
• NM_002361.4:c.1324G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002361.4(MAG):​c.1324G>T​(p.Val442Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,668 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict 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: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: MAG NM_002361.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.74

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2000204).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAG	NM_002361.4	c.1324G>T	p.Val442Leu	missense_variant	Exon 8 of 11	ENST00000392213.8	NP_002352.1
MAG	NM_001199216.2	c.1249G>T	p.Val417Leu	missense_variant	Exon 8 of 11		NP_001186145.1
MAG	NM_080600.3	c.1324G>T	p.Val442Leu	missense_variant	Exon 8 of 12		NP_542167.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAG	ENST00000392213.8	c.1324G>T	p.Val442Leu	missense_variant	Exon 8 of 11	1	NM_002361.4	ENSP00000376048.2
MAG	ENST00000537831.2	c.1249G>T	p.Val417Leu	missense_variant	Exon 8 of 11	1		ENSP00000440695.1
MAG	ENST00000361922.8	c.1324G>T	p.Val442Leu	missense_variant	Exon 8 of 12	1		ENSP00000355234.4
MAG	ENST00000593348.1	n.161G>T		non_coding_transcript_exon_variant	Exon 1 of 3	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461668 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 727158

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.082	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	23
DANN	Benign	0.88
DEOGEN2	Benign	0.050	T;.;.
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.075
FATHMM_MKL	Benign	0.75	D
LIST_S2	Uncertain	0.86	D;D;D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.20	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N;N;.
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	1.2	N;N;N
REVEL	Benign	0.11
Sift	Benign	0.89	T;T;T
Sift4G	Benign	0.47	T;T;T
Polyphen		0.066	B;.;.
Vest4		0.43
MutPred		0.45		Loss of catalytic residue at V442 (P = 0.0588);Loss of catalytic residue at V442 (P = 0.0588);.;
MVP		0.75
MPC		0.43
ClinPred		0.68	D
GERP RS		4.8
Varity_R		0.065
gMVP		0.75

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-35800869;