chr5-180792304-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002406.4(MGAT1):​c.668G>A​(p.Arg223Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.098 in 1,609,498 control chromosomes in the GnomAD database, including 8,981 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 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. R223W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.13 ( 1446 hom., cov: 33)
Exomes 𝑓: 0.095 ( 7535 hom. )

Consequence

MGAT1
NM_002406.4 missense

Scores

1
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.16

Publications

32 publications found
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 was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0017002821).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.198 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MGAT1NM_002406.4 linkc.668G>A p.Arg223Gln 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.668G>A p.Arg223Gln missense_variant Exon 2 of 2 1 NM_002406.4 ENSP00000311888.4 P26572

Frequencies

GnomAD3 genomes
AF:
0.127
AC:
19317
AN:
152132
Hom.:
1433
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.201
Gnomad AMI
AF:
0.240
Gnomad AMR
AF:
0.0842
Gnomad ASJ
AF:
0.0726
Gnomad EAS
AF:
0.206
Gnomad SAS
AF:
0.174
Gnomad FIN
AF:
0.116
Gnomad MID
AF:
0.133
Gnomad NFE
AF:
0.0849
Gnomad OTH
AF:
0.132
GnomAD2 exomes
AF:
0.112
AC:
27428
AN:
245866
AF XY:
0.113
show subpopulations
Gnomad AFR exome
AF:
0.210
Gnomad AMR exome
AF:
0.0687
Gnomad ASJ exome
AF:
0.0731
Gnomad EAS exome
AF:
0.230
Gnomad FIN exome
AF:
0.107
Gnomad NFE exome
AF:
0.0835
Gnomad OTH exome
AF:
0.0978
GnomAD4 exome
AF:
0.0950
AC:
138390
AN:
1457248
Hom.:
7535
Cov.:
36
AF XY:
0.0967
AC XY:
69996
AN XY:
724150
show subpopulations
African (AFR)
AF:
0.205
AC:
6860
AN:
33404
American (AMR)
AF:
0.0715
AC:
3191
AN:
44658
Ashkenazi Jewish (ASJ)
AF:
0.0759
AC:
1978
AN:
26062
East Asian (EAS)
AF:
0.209
AC:
8250
AN:
39554
South Asian (SAS)
AF:
0.157
AC:
13525
AN:
86166
European-Finnish (FIN)
AF:
0.105
AC:
5481
AN:
52282
Middle Eastern (MID)
AF:
0.121
AC:
695
AN:
5752
European-Non Finnish (NFE)
AF:
0.0832
AC:
92248
AN:
1109190
Other (OTH)
AF:
0.102
AC:
6162
AN:
60180
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.500
Heterozygous variant carriers
0
8623
17245
25868
34490
43113
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
3636
7272
10908
14544
18180
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.127
AC:
19381
AN:
152250
Hom.:
1446
Cov.:
33
AF XY:
0.129
AC XY:
9628
AN XY:
74446
show subpopulations
African (AFR)
AF:
0.202
AC:
8389
AN:
41538
American (AMR)
AF:
0.0842
AC:
1289
AN:
15312
Ashkenazi Jewish (ASJ)
AF:
0.0726
AC:
252
AN:
3470
East Asian (EAS)
AF:
0.206
AC:
1062
AN:
5158
South Asian (SAS)
AF:
0.174
AC:
838
AN:
4828
European-Finnish (FIN)
AF:
0.116
AC:
1229
AN:
10608
Middle Eastern (MID)
AF:
0.146
AC:
43
AN:
294
European-Non Finnish (NFE)
AF:
0.0849
AC:
5778
AN:
68020
Other (OTH)
AF:
0.134
AC:
283
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.499
Heterozygous variant carriers
0
883
1765
2648
3530
4413
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
208
416
624
832
1040
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.0964
Hom.:
2765
Bravo
AF:
0.129
TwinsUK
AF:
0.0839
AC:
311
ALSPAC
AF:
0.0851
AC:
328
ESP6500AA
AF:
0.200
AC:
877
ESP6500EA
AF:
0.0797
AC:
684
ExAC
AF:
0.114
AC:
13841
Asia WGS
AF:
0.189
AC:
655
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.057
BayesDel_addAF
Benign
-0.62
T
BayesDel_noAF
Benign
-0.52
CADD
Benign
18
DANN
Benign
0.83
DEOGEN2
Benign
0.29
T;T;T;T;T
Eigen
Benign
-0.56
Eigen_PC
Benign
-0.36
FATHMM_MKL
Benign
0.34
N
LIST_S2
Benign
0.47
.;.;.;T;.
MetaRNN
Benign
0.0017
T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
-0.28
N;N;N;N;N
PhyloP100
3.2
PrimateAI
Uncertain
0.50
T
PROVEAN
Benign
-0.12
N;N;N;N;N
REVEL
Benign
0.25
Sift
Benign
0.63
T;T;T;T;T
Sift4G
Benign
0.60
T;T;T;T;T
Polyphen
0.0
B;B;B;B;B
Vest4
0.019
MPC
0.91
ClinPred
0.0082
T
GERP RS
5.6
Varity_R
0.026
gMVP
0.28
Mutation Taster
=100/0
polymorphism (auto)

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

Other links and lift over

dbSNP: rs7726005; hg19: chr5-180219304; COSMIC: COSV57133090; COSMIC: COSV57133090; API