2-134454758-G-T

Variant names:

• chr2-134454758-G-T
• rs539588
• NM_002410.5:c.*5911G>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002410.5(MGAT5):​c.*5911G>T variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.548 in 151,962 control chromosomes in the GnomAD database, including 25,267 homozygotes. 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: 𝑓 0.55 (25263 hom., cov: 31)
  • Exomes 𝑓: 0.50 (4 hom.)
• Consequence: MGAT5 NM_002410.5 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.94

Genes affected

MGAT5 (HGNC:7049): (alpha-1,6-mannosylglycoprotein 6-beta-N-acetylglucosaminyltransferase) The protein encoded by this gene belongs to the glycosyltransferase family. It catalyzes the addition of beta-1,6-N-acetylglucosamine to the alpha-linked mannose of biantennary N-linked oligosaccharides present on the newly synthesized glycoproteins. It is one of the most important enzymes involved in the regulation of the biosynthesis of glycoprotein oligosaccharides. Alterations of the oligosaccharides on cell surface glycoproteins cause significant changes in the adhesive or migratory behavior of a cell. Increase in the activity of this enzyme has been correlated with the progression of invasive malignancies. [provided by RefSeq, Oct 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.95 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MGAT5	NM_002410.5	c.*5911G>T		downstream_gene_variant		ENST00000281923.4	NP_002401.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MGAT5	ENST00000281923.4	c.*5911G>T		downstream_gene_variant		1	NM_002410.5	ENSP00000281923.2
MGAT5	ENST00000409645.5	c.*5911G>T		downstream_gene_variant		5		ENSP00000386377.1

Frequencies

GnomAD3 genomes AF: 0.547 AC: 83103 AN: 151812 Hom.: 25192 Cov.: 31

Gnomad AFR AF: 0.723

Gnomad AMI AF: 0.371

Gnomad AMR AF: 0.635

Gnomad ASJ AF: 0.590

Gnomad EAS AF: 0.973

Gnomad SAS AF: 0.764

Gnomad FIN AF: 0.360

Gnomad MID AF: 0.713

Gnomad NFE AF: 0.402

Gnomad OTH AF: 0.559

GnomAD4 exome AF: 0.500 AC: 15 AN: 30 Hom.: 4 AF XY: 0.500 AC XY: 12 AN XY: 24

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.545

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.548 AC: 83236 AN: 151932 Hom.: 25263 Cov.: 31 AF XY: 0.555 AC XY: 41250 AN XY: 74266

Gnomad4 AFR AF: 0.723

Gnomad4 AMR AF: 0.636

Gnomad4 ASJ AF: 0.590

Gnomad4 EAS AF: 0.973

Gnomad4 SAS AF: 0.765

Gnomad4 FIN AF: 0.360

Gnomad4 NFE AF: 0.402

Gnomad4 OTH AF: 0.565

Alfa AF: 0.447 Hom.: 22625

Bravo AF: 0.577

Asia WGS AF: 0.854 AC: 2968 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.0040
DANN	Benign	0.60

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs539588; hg19: chr2-135212329;