chr2-98678420-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_012214.3(MGAT4A):c.146G>A(p.Arg49Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000126 in 1,589,842 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 (★).
Frequency
Genomes: 𝑓 0.000053 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000083 ( 0 hom. )
Consequence
MGAT4A
NM_012214.3 missense
NM_012214.3 missense
Scores
1
4
13
Clinical Significance
Conservation
PhyloP100: 5.68
Genes affected
MGAT4A (HGNC:7047): (alpha-1,3-mannosyl-glycoprotein 4-beta-N-acetylglucosaminyltransferase A) This gene encodes a key glycosyltransferase that regulates the formation of tri- and multiantennary branching structures in the Golgi apparatus. The encoded protein, in addition to the related isoenzyme B, catalyzes the transfer of N-acetylglucosamine (GlcNAc) from UDP-GlcNAc in a beta-1,4 linkage to the Man-alpha-1,3-Man-beta-1,4-GlcNAc arm of R-Man-alpha-1,6(GlcNAc-beta-1,2-Man-alpha-1,3)Man-beta-1,4-GlcNAc-beta-1,4-GlcNAc-beta-1-Asn. The encoded protein may play a role in regulating the availability of serum glycoproteins, oncogenesis, and differentiation. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.3630811).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MGAT4A | NM_012214.3 | c.146G>A | p.Arg49Gln | missense_variant | 3/16 | ENST00000393487.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MGAT4A | ENST00000393487.6 | c.146G>A | p.Arg49Gln | missense_variant | 3/16 | 5 | NM_012214.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000528 AC: 8AN: 151600Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.0000160 AC: 4AN: 249290Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 134860
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GnomAD4 exome AF: 0.00000834 AC: 12AN: 1438242Hom.: 0 Cov.: 30 AF XY: 0.0000126 AC XY: 9AN XY: 715510
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GnomAD4 genome ? AF: 0.0000528 AC: 8AN: 151600Hom.: 0 Cov.: 31 AF XY: 0.0000270 AC XY: 2AN XY: 74012
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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 | May 31, 2023 | The c.146G>A (p.R49Q) alteration is located in exon 3 (coding exon 2) of the MGAT4A gene. This alteration results from a G to A substitution at nucleotide position 146, causing the arginine (R) at amino acid position 49 to be replaced by a glutamine (Q). 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
Uncertain
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T;T;T
Eigen
Uncertain
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L;L
MutationTaster
Benign
D;D;D
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N
REVEL
Benign
Sift
Benign
T;T;T
Sift4G
Benign
T;T;T
Polyphen
D;D;D
Vest4
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