chr22-39488662-G-A

Position:

• chr22-39488662-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM2 PP3_Moderate BP6

The NM_002409.5(MGAT3):​c.1315G>A​(p.Asp439Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MGAT3 NM_002409.5 missense
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 9.40

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

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.935
• BP6: Variant 22-39488662-G-A is Benign according to our data. Variant chr22-39488662-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2681399.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MGAT3	NM_002409.5	c.1315G>A	p.Asp439Asn	missense_variant	2/2	ENST00000341184.7
MGAT3	NM_001098270.2	c.1315G>A	p.Asp439Asn	missense_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MGAT3	ENST00000341184.7	c.1315G>A	p.Asp439Asn	missense_variant	2/2	1	NM_002409.5	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

EBV-positive nodal T- and NK-cell lymphoma Benign:1

Likely benign, no assertion criteria provided

research

Department of Clinical Pathology, School of Medicine, Fujita Health University

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Benign	-0.073	T
BayesDel_noAF	Benign	-0.34
CADD	Pathogenic	33
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.79	D
Eigen	Pathogenic	0.89
Eigen_PC	Pathogenic	0.88
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.0099	T
MetaRNN	Pathogenic	0.94	D
MetaSVM	Uncertain	-0.15	T
MutationAssessor	Pathogenic	3.1	M
MutationTaster	Benign	1.0	D
PrimateAI	Pathogenic	0.85	D
PROVEAN	Uncertain	-2.6	D
REVEL	Uncertain	0.35
Sift	Benign	0.093	T
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.71
MutPred		0.85		Gain of catalytic residue at D439 (P = 0.0607);
MVP		0.21
MPC		2.2
ClinPred		0.97	D
GERP RS		5.7
Varity_R		0.34
gMVP		0.90

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-39884667; COSMIC: COSV105829752; COSMIC: COSV105829752;