22-39459878-C-T

Variant names:

• chr22-39459878-C-T
• rs738289
• NM_002409.5:c.-2+2321C>T

Variant summary

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

The NM_002409.5(MGAT3):​c.-2+2321C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.785 in 152,250 control chromosomes in the GnomAD database, including 47,305 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 0.78 (47305 hom., cov: 34)
• Consequence: MGAT3 NM_002409.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.60
• Publications: 10 publications found

Genes affected

MGAT3 (HGNC:7046): (beta-1,4-mannosyl-glycoprotein 4-beta-N-acetylglucosaminyltransferase) There are believed to be over 100 different glycosyltransferases involved in the synthesis of protein-bound and lipid-bound oligosaccharides. The enzyme encoded by this gene transfers a GlcNAc residue to the beta-linked mannose of the trimannosyl core of N-linked oligosaccharides and produces a bisecting GlcNAc. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MGAT3	NM_002409.5	c.-2+2321C>T		intron_variant	Intron 1 of 1	ENST00000341184.7	NP_002400.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MGAT3	ENST00000341184.7	c.-2+2321C>T		intron_variant	Intron 1 of 1	1	NM_002409.5	ENSP00000345270.6

Frequencies

GnomAD3 genomes AF: 0.784 AC: 119347 AN: 152132 Hom.: 47245 Cov.: 34

Gnomad AFR AF: 0.856

Gnomad AMI AF: 0.692

Gnomad AMR AF: 0.813

Gnomad ASJ AF: 0.688

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.879

Gnomad FIN AF: 0.729

Gnomad MID AF: 0.623

Gnomad NFE AF: 0.728

Gnomad OTH AF: 0.756

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

GnomAD4 genome AF: 0.785 AC: 119464 AN: 152250 Hom.: 47305 Cov.: 34 AF XY: 0.786 AC XY: 58521 AN XY: 74440

African (AFR) AF: 0.856 AC: 35568 AN: 41566

American (AMR) AF: 0.814 AC: 12446 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.688 AC: 2388 AN: 3472

East Asian (EAS) AF: 0.998 AC: 5160 AN: 5172

South Asian (SAS) AF: 0.879 AC: 4243 AN: 4828

European-Finnish (FIN) AF: 0.729 AC: 7726 AN: 10594

Middle Eastern (MID) AF: 0.619 AC: 182 AN: 294

European-Non Finnish (NFE) AF: 0.728 AC: 49519 AN: 68004

Other (OTH) AF: 0.758 AC: 1602 AN: 2114

Alfa AF: 0.738 Hom.: 52414

Bravo AF: 0.793

Asia WGS AF: 0.938 AC: 3260 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.31
DANN	Benign	0.85
PhyloP100		-1.6
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: rs738289; hg19: chr22-39855883;