rs12467609

Variant names:

• chr2-134385716-C-T
• rs12467609
• NM_002410.5:c.1381-17272C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002410.5(MGAT5):​c.1381-17272C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.606 in 151,930 control chromosomes in the GnomAD database, including 28,135 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 0.61 (28135 hom., cov: 32)
• Consequence: MGAT5 NM_002410.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.698
• Publications: 9 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=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.616 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MGAT5	NM_002410.5	c.1381-17272C>T		intron_variant	Intron 10 of 15	ENST00000281923.4	NP_002401.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MGAT5	ENST00000281923.4	c.1381-17272C>T		intron_variant	Intron 10 of 15	1	NM_002410.5	ENSP00000281923.2
MGAT5	ENST00000409645.5	c.1381-17272C>T		intron_variant	Intron 11 of 16	5		ENSP00000386377.1

Frequencies

GnomAD3 genomes AF: 0.606 AC: 91998 AN: 151812 Hom.: 28088 Cov.: 32

Gnomad AFR AF: 0.584

Gnomad AMI AF: 0.579

Gnomad AMR AF: 0.616

Gnomad ASJ AF: 0.396

Gnomad EAS AF: 0.582

Gnomad SAS AF: 0.606

Gnomad FIN AF: 0.679

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.621

Gnomad OTH AF: 0.566

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.606 AC: 92107 AN: 151930 Hom.: 28135 Cov.: 32 AF XY: 0.608 AC XY: 45181 AN XY: 74254

African (AFR) AF: 0.584 AC: 24185 AN: 41382

American (AMR) AF: 0.616 AC: 9416 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.396 AC: 1374 AN: 3470

East Asian (EAS) AF: 0.583 AC: 3010 AN: 5166

South Asian (SAS) AF: 0.606 AC: 2922 AN: 4822

European-Finnish (FIN) AF: 0.679 AC: 7164 AN: 10556

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.621 AC: 42214 AN: 67948

Other (OTH) AF: 0.570 AC: 1199 AN: 2104

Alfa AF: 0.607 Hom.: 38321

Bravo AF: 0.596

Asia WGS AF: 0.615 AC: 2135 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.25
DANN	Benign	0.53
PhyloP100		-0.70
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: rs12467609; hg19: chr2-135143287;