2-134403184-G-A

Variant names:

• chr2-134403184-G-A
• rs3748900
• NM_002410.5:c.1530+47G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002410.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MGAT5	NM_002410.5	MANE Select	c.1530+47G>A		intron	N/A	NP_002401.1
	MGAT5	NM_001371457.1		c.1530+47G>A		intron	N/A	NP_001358386.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MGAT5	ENST00000281923.4	TSL:1 MANE Select	c.1530+47G>A		intron	N/A	ENSP00000281923.2
	MGAT5	ENST00000409645.5	TSL:5	c.1530+47G>A		intron	N/A	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

GnomAD2 exomes AF: 0.342 AC: 64325 AN: 188124 AF XY: 0.347

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 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

African (AFR) AF: 0.239 AC: 6959 AN: 29124

American (AMR) AF: 0.379 AC: 9569 AN: 25230

Ashkenazi Jewish (ASJ) AF: 0.351 AC: 8297 AN: 23640

East Asian (EAS) AF: 0.465 AC: 16791 AN: 36132

South Asian (SAS) AF: 0.453 AC: 33644 AN: 74342

European-Finnish (FIN) AF: 0.295 AC: 15496 AN: 52510

Middle Eastern (MID) AF: 0.312 AC: 1721 AN: 5514

European-Non Finnish (NFE) AF: 0.314 AC: 338153 AN: 1075446

Other (OTH) AF: 0.327 AC: 18562 AN: 56806

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

African (AFR) AF: 0.243 AC: 10073 AN: 41492

American (AMR) AF: 0.380 AC: 5798 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.358 AC: 1241 AN: 3466

East Asian (EAS) AF: 0.428 AC: 2210 AN: 5162

South Asian (SAS) AF: 0.464 AC: 2233 AN: 4816

European-Finnish (FIN) AF: 0.293 AC: 3092 AN: 10564

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.322 AC: 21876 AN: 67958

Other (OTH) AF: 0.321 AC: 680 AN: 2116

Alfa AF: 0.331 Hom.: 7682

Bravo AF: 0.314

Asia WGS AF: 0.427 AC: 1486 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.7
DANN	Benign	0.72
PhyloP100		0.21
Mutation Taster		=100/0	polymorphism (auto)

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