chr2-134243967-T-C

Position:

• chr2-134243967-T-C

Variant summary

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

The NM_001371457.1(MGAT5):​c.-142-10295T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.654 in 152,010 control chromosomes in the GnomAD database, including 33,667 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 0.65 (33667 hom., cov: 32)
• Consequence: MGAT5 NM_001371457.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.227

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=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.735 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MGAT5	NM_001371457.1	c.-142-10295T>C		intron_variant
MGAT5	XM_005263669.6	c.-139-10298T>C		intron_variant
MGAT5	XM_006712534.4	c.-359-6083T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MGAT5	ENST00000409645.5	c.-142-10295T>C		intron_variant		5		P1
MGAT5	ENST00000468758.1	n.310-9128T>C		intron_variant, non_coding_transcript_variant		5
MGAT5	ENST00000481801.5	n.310-10298T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.654 AC: 99332 AN: 151894 Hom.: 33635 Cov.: 32

Gnomad AFR AF: 0.478

Gnomad AMI AF: 0.624

Gnomad AMR AF: 0.665

Gnomad ASJ AF: 0.685

Gnomad EAS AF: 0.597

Gnomad SAS AF: 0.686

Gnomad FIN AF: 0.770

Gnomad MID AF: 0.654

Gnomad NFE AF: 0.741

Gnomad OTH AF: 0.657

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

GnomAD4 genome AF: 0.654 AC: 99420 AN: 152010 Hom.: 33667 Cov.: 32 AF XY: 0.657 AC XY: 48791 AN XY: 74286

Gnomad4 AFR AF: 0.479

Gnomad4 AMR AF: 0.665

Gnomad4 ASJ AF: 0.685

Gnomad4 EAS AF: 0.596

Gnomad4 SAS AF: 0.688

Gnomad4 FIN AF: 0.770

Gnomad4 NFE AF: 0.741

Gnomad4 OTH AF: 0.656

Alfa AF: 0.685 Hom.: 5933

Bravo AF: 0.637

Asia WGS AF: 0.670 AC: 2331 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	15
DANN	Benign	0.76

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: rs1257189; hg19: chr2-135001538;