rs3748900

Positions:

• chr2-134403184-G-A

Variant summary

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

The NM_002410.5(MGAT5):​c.1530+47G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.325 in 1,530,786 control chromosomes in the GnomAD database, including 82,969 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 0.31 (7725 hom., cov: 33)
  • Exomes 𝑓: 0.33 (75244 hom.)
• Consequence: MGAT5 NM_002410.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.206

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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.448 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MGAT5	NM_002410.5	c.1530+47G>A		intron_variant		ENST00000281923.4	NP_002401.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MGAT5	ENST00000281923.4	c.1530+47G>A		intron_variant		1	NM_002410.5	ENSP00000281923.2
MGAT5	ENST00000409645.5	c.1530+47G>A		intron_variant		5		ENSP00000386377.1

Frequencies

GnomAD3 genomes AF: 0.313 AC: 47551 AN: 151924 Hom.: 7717 Cov.: 33

Gnomad AFR AF: 0.243

Gnomad AMI AF: 0.329

Gnomad AMR AF: 0.379

Gnomad ASJ AF: 0.358

Gnomad EAS AF: 0.428

Gnomad SAS AF: 0.462

Gnomad FIN AF: 0.293

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.322

Gnomad OTH AF: 0.320

GnomAD3 exomes AF: 0.342 AC: 64325 AN: 188124 Hom.: 11188 AF XY: 0.347 AC XY: 35999 AN XY: 103866

Gnomad AFR exome AF: 0.237

Gnomad AMR exome AF: 0.382

Gnomad ASJ exome AF: 0.353

Gnomad EAS exome AF: 0.432

Gnomad SAS exome AF: 0.457

Gnomad FIN exome AF: 0.297

Gnomad NFE exome AF: 0.321

Gnomad OTH exome AF: 0.337

GnomAD4 exome AF: 0.326 AC: 449192 AN: 1378744 Hom.: 75244 Cov.: 26 AF XY: 0.330 AC XY: 225358 AN XY: 682350

Gnomad4 AFR exome AF: 0.239

Gnomad4 AMR exome AF: 0.379

Gnomad4 ASJ exome AF: 0.351

Gnomad4 EAS exome AF: 0.465

Gnomad4 SAS exome AF: 0.453

Gnomad4 FIN exome AF: 0.295

Gnomad4 NFE exome AF: 0.314

Gnomad4 OTH exome AF: 0.327

GnomAD4 genome AF: 0.313 AC: 47588 AN: 152042 Hom.: 7725 Cov.: 33 AF XY: 0.316 AC XY: 23503 AN XY: 74326

Gnomad4 AFR AF: 0.243

Gnomad4 AMR AF: 0.380

Gnomad4 ASJ AF: 0.358

Gnomad4 EAS AF: 0.428

Gnomad4 SAS AF: 0.464

Gnomad4 FIN AF: 0.293

Gnomad4 NFE AF: 0.322

Gnomad4 OTH AF: 0.321

Alfa AF: 0.331 Hom.: 5859

Bravo AF: 0.314

Asia WGS AF: 0.427 AC: 1486 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.7
DANN	Benign	0.72

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: rs3748900; hg19: chr2-135160755; COSMIC: COSV56094963;