rs1257168

chr2-134206321-A-Gchr2-134206321-A-T

Variant summary

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

The NM_001371457.1(MGAT5):c.-142-47941A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.661 in 152,152 control chromosomes in the GnomAD database, including 34,950 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 0.66 (34950 hom., cov: 32)
• Consequence: MGAT5 NM_001371457.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.874

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 (AFR) allele frequency at 95% confidence interval = 0.858 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MGAT5	NM_001371457.1	c.-142-47941A>G		intron_variant
MGAT5	XM_005263669.6	c.-139-47944A>G		intron_variant
MGAT5	XM_006712534.4	c.-360+16073A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MGAT5	ENST00000409645.5	c.-142-47941A>G		intron_variant		5		P1
MGAT5	ENST00000468758.1	n.310-46774A>G		intron_variant, non_coding_transcript_variant		5
MGAT5	ENST00000481801.5	n.310-47944A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.660 AC: 100363 AN: 152034 Hom.: 34873 Cov.: 32

Gnomad AFR AF: 0.866

Gnomad AMI AF: 0.574

Gnomad AMR AF: 0.674

Gnomad ASJ AF: 0.741

Gnomad EAS AF: 0.835

Gnomad SAS AF: 0.730

Gnomad FIN AF: 0.495

Gnomad MID AF: 0.718

Gnomad NFE AF: 0.535

Gnomad OTH AF: 0.689

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

GnomAD4 genome AF: 0.661 AC: 100507 AN: 152152 Hom.: 34950 Cov.: 32 AF XY: 0.661 AC XY: 49175 AN XY: 74372

Gnomad4 AFR AF: 0.866

Gnomad4 AMR AF: 0.674

Gnomad4 ASJ AF: 0.741

Gnomad4 EAS AF: 0.835

Gnomad4 SAS AF: 0.731

Gnomad4 FIN AF: 0.495

Gnomad4 NFE AF: 0.535

Gnomad4 OTH AF: 0.692

Alfa AF: 0.605 Hom.: 3578

Bravo AF: 0.688

Asia WGS AF: 0.824 AC: 2863 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	0.59
Dann	Benign	0.46

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: rs1257168; hg19: chr2-134963892;