rs144433730

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_002406.4(MGAT1):​c.1133G>T​(p.Arg378Leu) 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 benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R378Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Consequence

MGAT1
NM_002406.4 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.592
Variant links:
Genes affected
MGAT1 (HGNC:7044): (alpha-1,3-mannosyl-glycoprotein 2-beta-N-acetylglucosaminyltransferase) There are believed to be over 100 different glycosyltransferases involved in the synthesis of protein-bound and lipid-bound oligosaccharides. UDP-N-acetylglucosamine:alpha-3-D-mannoside beta-1,2-N-acetylglucosaminyltransferase I is a medial-Golgi enzyme essential for the synthesis of hybrid and complex N-glycans. The protein, encoded by a single exon, shows typical features of a type II transmembrane protein. The protein is believed to be essential for normal embryogenesis. Several variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.06049174).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MGAT1NM_002406.4 linkc.1133G>T p.Arg378Leu missense_variant Exon 2 of 2 ENST00000307826.5 NP_002397.2 P26572

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MGAT1ENST00000307826.5 linkc.1133G>T p.Arg378Leu missense_variant Exon 2 of 2 1 NM_002406.4 ENSP00000311888.4 P26572

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
36
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.13
BayesDel_addAF
Benign
-0.10
T
BayesDel_noAF
Benign
-0.38
CADD
Benign
6.2
DANN
Benign
0.75
DEOGEN2
Benign
0.26
T;T;T;T;T
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.085
N
LIST_S2
Benign
0.78
.;.;.;T;.
M_CAP
Benign
0.042
D
MetaRNN
Benign
0.060
T;T;T;T;T
MetaSVM
Benign
-0.93
T
MutationAssessor
Benign
0.39
N;N;N;N;N
PrimateAI
Benign
0.42
T
PROVEAN
Benign
1.1
N;N;N;N;N
REVEL
Benign
0.19
Sift
Benign
0.46
T;T;T;T;T
Sift4G
Benign
0.73
T;T;T;T;T
Polyphen
0.0
B;B;B;B;B
Vest4
0.091
MutPred
0.35
Loss of solvent accessibility (P = 0.0022);Loss of solvent accessibility (P = 0.0022);Loss of solvent accessibility (P = 0.0022);Loss of solvent accessibility (P = 0.0022);Loss of solvent accessibility (P = 0.0022);
MVP
0.21
MPC
0.97
ClinPred
0.035
T
GERP RS
2.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.029
gMVP
0.42

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: chr5-180218839; API