rs746679758

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_002406.4(MGAT1):​c.1154G>T​(p.Arg385Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. R385Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

MGAT1
NM_002406.4 missense

Scores

9
8
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.90
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.973

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MGAT1NM_002406.4 linkc.1154G>T p.Arg385Leu 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.1154G>T p.Arg385Leu missense_variant Exon 2 of 2 1 NM_002406.4 ENSP00000311888.4 P26572

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461888
Hom.:
0
Cov.:
36
AF XY:
0.00
AC XY:
0
AN XY:
727248
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.73
BayesDel_addAF
Pathogenic
0.43
D
BayesDel_noAF
Pathogenic
0.37
CADD
Pathogenic
28
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.78
D;D;D;D;D
Eigen
Pathogenic
0.81
Eigen_PC
Pathogenic
0.77
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Benign
0.85
.;.;.;T;.
M_CAP
Uncertain
0.23
D
MetaRNN
Pathogenic
0.97
D;D;D;D;D
MetaSVM
Uncertain
0.74
D
MutationAssessor
Uncertain
2.3
M;M;M;M;M
PrimateAI
Uncertain
0.78
T
PROVEAN
Pathogenic
-6.0
D;D;D;D;D
REVEL
Pathogenic
0.85
Sift
Uncertain
0.0020
D;D;D;D;D
Sift4G
Uncertain
0.0050
D;D;D;D;D
Polyphen
1.0
D;D;D;D;D
Vest4
0.86
MutPred
0.91
Loss of MoRF binding (P = 0.0215);Loss of MoRF binding (P = 0.0215);Loss of MoRF binding (P = 0.0215);Loss of MoRF binding (P = 0.0215);Loss of MoRF binding (P = 0.0215);
MVP
0.95
MPC
2.1
ClinPred
0.99
D
GERP RS
4.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.62
gMVP
0.85

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: chr5-180218818; API