chr22-39487571-A-G
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_002409.5(MGAT3):āc.224A>Gā(p.Tyr75Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000435 in 1,610,020 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.0000067 ( 0 hom., cov: 32)
Exomes š: 0.0000041 ( 0 hom. )
Consequence
MGAT3
NM_002409.5 missense
NM_002409.5 missense
Scores
4
15
Clinical Significance
Conservation
PhyloP100: 3.86
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.21152678).
BS2
High AC in GnomAdExome4 at 6 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MGAT3 | NM_002409.5 | c.224A>G | p.Tyr75Cys | missense_variant | 2/2 | ENST00000341184.7 | |
MGAT3 | NM_001098270.2 | c.224A>G | p.Tyr75Cys | missense_variant | 1/1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MGAT3 | ENST00000341184.7 | c.224A>G | p.Tyr75Cys | missense_variant | 2/2 | 1 | NM_002409.5 | P1 | |
MGAT3 | ENST00000429402.1 | c.224A>G | p.Tyr75Cys | missense_variant | 2/2 | 4 | |||
MGAT3 | ENST00000418314.1 | c.308A>G | p.Tyr103Cys | missense_variant | 3/3 | 4 |
Frequencies
GnomAD3 genomes AF: 0.00000666 AC: 1AN: 150218Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000806 AC: 2AN: 248038Hom.: 0 AF XY: 0.00000744 AC XY: 1AN XY: 134444
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GnomAD4 exome AF: 0.00000411 AC: 6AN: 1459802Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1AN XY: 726332
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GnomAD4 genome AF: 0.00000666 AC: 1AN: 150218Hom.: 0 Cov.: 32 AF XY: 0.0000137 AC XY: 1AN XY: 73212
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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 | Dec 27, 2023 | The c.224A>G (p.Y75C) alteration is located in exon 2 (coding exon 1) of the MGAT3 gene. This alteration results from a A to G substitution at nucleotide position 224, causing the tyrosine (Y) at amino acid position 75 to be replaced by a cysteine (C). 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
Uncertain
DEOGEN2
Benign
T;T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;.
MutationTaster
Benign
N
PrimateAI
Uncertain
T
PROVEAN
Benign
N;D;D
REVEL
Benign
Sift
Benign
D;D;D
Sift4G
Benign
T;T;D
Polyphen
D;.;.
Vest4
MutPred
Loss of phosphorylation at Y75 (P = 0.0144);Loss of phosphorylation at Y75 (P = 0.0144);.;
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at