22-39488526-A-C

Position:

• chr22-39488526-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_002409.5(MGAT3):​c.1179A>C​(p.Arg393Ser) variant causes a missense change involving the alteration of a non-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 Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MGAT3 NM_002409.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -3.65

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.905

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MGAT3	NM_002409.5	c.1179A>C	p.Arg393Ser	missense_variant	2/2	ENST00000341184.7
MGAT3	NM_001098270.2	c.1179A>C	p.Arg393Ser	missense_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MGAT3	ENST00000341184.7	c.1179A>C	p.Arg393Ser	missense_variant	2/2	1	NM_002409.5	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 07, 2023

The c.1179A>C (p.R393S) alteration is located in exon 2 (coding exon 1) of the MGAT3 gene. This alteration results from a A to C substitution at nucleotide position 1179, causing the arginine (R) at amino acid position 393 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Pathogenic	0.14
CADD	Benign	2.3
DANN	Benign	0.90
DEOGEN2	Benign	0.33	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.064	N
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.0065	T
MetaRNN	Pathogenic	0.90	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Pathogenic	3.0	M
MutationTaster	Benign	0.99	N
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-1.2	N
REVEL	Uncertain	0.30
Sift	Benign	0.16	T
Sift4G	Benign	0.11	T
Polyphen		0.82	P
Vest4		0.75
MutPred		0.86		Loss of methylation at R393 (P = 0.0284);
MVP		0.10
MPC		1.8
ClinPred		0.27	T
GERP RS		-11
Varity_R		0.28
gMVP		0.99

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: chr22-39884531;