chr22-39487969-G-A
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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):c.622G>A(p.Val208Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000031 in 1,612,250 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000032 ( 1 hom. )
Consequence
MGAT3
NM_002409.5 missense
NM_002409.5 missense
Scores
1
2
16
Clinical Significance
Conservation
PhyloP100: 5.44
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=0.09368402).
BS2
High AC in GnomAdExome4 at 47 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MGAT3 | NM_002409.5 | c.622G>A | p.Val208Ile | missense_variant | 2/2 | ENST00000341184.7 | |
MGAT3 | NM_001098270.2 | c.622G>A | p.Val208Ile | missense_variant | 1/1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MGAT3 | ENST00000341184.7 | c.622G>A | p.Val208Ile | missense_variant | 2/2 | 1 | NM_002409.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152236Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000612 AC: 15AN: 245156Hom.: 0 AF XY: 0.0000897 AC XY: 12AN XY: 133766
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GnomAD4 exome AF: 0.0000322 AC: 47AN: 1459896Hom.: 1 Cov.: 34 AF XY: 0.0000454 AC XY: 33AN XY: 726332
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GnomAD4 genome AF: 0.0000197 AC: 3AN: 152354Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74498
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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 | Mar 04, 2024 | The c.622G>A (p.V208I) alteration is located in exon 2 (coding exon 1) of the MGAT3 gene. This alteration results from a G to A substitution at nucleotide position 622, causing the valine (V) at amino acid position 208 to be replaced by an isoleucine (I). 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
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
MutPred
Loss of sheet (P = 0.0315);
MVP
MPC
ClinPred
T
GERP RS
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