22-39487922-A-C
Position:
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_002409.5(MGAT3):āc.575A>Cā(p.Asn192Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000106 in 1,606,712 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000033 ( 0 hom., cov: 32)
Exomes š: 0.0000083 ( 0 hom. )
Consequence
MGAT3
NM_002409.5 missense
NM_002409.5 missense
Scores
1
1
17
Clinical Significance
Conservation
PhyloP100: 4.92
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.18173134).
BS2
High AC in GnomAd4 at 5 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MGAT3 | NM_002409.5 | c.575A>C | p.Asn192Thr | missense_variant | 2/2 | ENST00000341184.7 | |
MGAT3 | NM_001098270.2 | c.575A>C | p.Asn192Thr | missense_variant | 1/1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MGAT3 | ENST00000341184.7 | c.575A>C | p.Asn192Thr | missense_variant | 2/2 | 1 | NM_002409.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152138Hom.: 0 Cov.: 32
GnomAD3 genomes
AF:
AC:
5
AN:
152138
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0000252 AC: 6AN: 237666Hom.: 0 AF XY: 0.00000769 AC XY: 1AN XY: 130018
GnomAD3 exomes
AF:
AC:
6
AN:
237666
Hom.:
AF XY:
AC XY:
1
AN XY:
130018
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000825 AC: 12AN: 1454456Hom.: 0 Cov.: 34 AF XY: 0.00000553 AC XY: 4AN XY: 723300
GnomAD4 exome
AF:
AC:
12
AN:
1454456
Hom.:
Cov.:
34
AF XY:
AC XY:
4
AN XY:
723300
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.0000328 AC: 5AN: 152256Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74456
GnomAD4 genome
AF:
AC:
5
AN:
152256
Hom.:
Cov.:
32
AF XY:
AC XY:
3
AN XY:
74456
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Bravo
AF:
ExAC
AF:
AC:
2
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 22, 2024 | The c.575A>C (p.N192T) 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 575, causing the asparagine (N) at amino acid position 192 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
B
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at