rs4953911

Positions:

• chr2-134311223-T-A
• chr2-134311223-T-C

Variant summary

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

The ENST00000281923.4(MGAT5):​c.407-6306T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.566 in 152,038 control chromosomes in the GnomAD database, including 26,656 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 0.57 (26656 hom., cov: 31)
• Consequence: MGAT5 ENST00000281923.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.228

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=-0.76).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.688 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MGAT5	NM_002410.5	c.407-6306T>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.407-6306T>A		intron_variant		1	NM_002410.5	ENSP00000281923	P1
MGAT5	ENST00000409645.5	c.407-6306T>A		intron_variant		5		ENSP00000386377	P1

Frequencies

GnomAD3 genomes AF: 0.567 AC: 86078 AN: 151920 Hom.: 26636 Cov.: 31

Gnomad AFR AF: 0.313

Gnomad AMI AF: 0.742

Gnomad AMR AF: 0.578

Gnomad ASJ AF: 0.424

Gnomad EAS AF: 0.563

Gnomad SAS AF: 0.553

Gnomad FIN AF: 0.779

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.693

Gnomad OTH AF: 0.551

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

GnomAD4 genome AF: 0.566 AC: 86127 AN: 152038 Hom.: 26656 Cov.: 31 AF XY: 0.569 AC XY: 42265 AN XY: 74300

Gnomad4 AFR AF: 0.313

Gnomad4 AMR AF: 0.579

Gnomad4 ASJ AF: 0.424

Gnomad4 EAS AF: 0.563

Gnomad4 SAS AF: 0.553

Gnomad4 FIN AF: 0.779

Gnomad4 NFE AF: 0.693

Gnomad4 OTH AF: 0.553

Alfa AF: 0.529 Hom.: 1767

Bravo AF: 0.541

Asia WGS AF: 0.542 AC: 1883 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	13
DANN	Benign	0.82

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: rs4953911; hg19: chr2-135068794;