Genetic Variant NM_002406.4:c.1133G>C (chr5-180791839-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_002406.4(MGAT1):c.1133G>C(p.Arg378Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000788 in 152,224 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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. R378W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 33)

Consequence

MGAT1
NM_002406.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.592

Publications

0 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]

MGAT1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.11932242).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002406.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MGAT1	NM_002406.4	MANE Select	c.1133G>C	p.Arg378Pro	missense	Exon 2 of 2	NP_002397.2	P26572
MGAT1	NM_001114617.2		c.1133G>C	p.Arg378Pro	missense	Exon 3 of 3	NP_001108089.1	P26572
MGAT1	NM_001114618.1		c.1133G>C	p.Arg378Pro	missense	Exon 3 of 3	NP_001108090.1	P26572

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MGAT1	ENST00000307826.5	TSL:1 MANE Select	c.1133G>C	p.Arg378Pro	missense	Exon 2 of 2	ENSP00000311888.4	P26572
MGAT1	ENST00000333055.8	TSL:2	c.1133G>C	p.Arg378Pro	missense	Exon 3 of 3	ENSP00000332073.3	P26572
MGAT1	ENST00000393340.7	TSL:2	c.1133G>C	p.Arg378Pro	missense	Exon 3 of 3	ENSP00000377010.3	P26572

Frequencies

GnomAD3 genomes

AF:

0.0000788

AC:

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000289

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000796

AC:

AN:

251398

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.0000788

AC:

AN:

152224

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.000289

AC:

AN:

41464

American (AMR)

AF:

0.00

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68034

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.0000712

Hom.:

Bravo

AF:

0.0000907

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000165

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.20

CADD

Benign

(source)

DANN

Benign

0.72

DEOGEN2

Benign

0.30

Eigen

Benign

-0.86

Eigen_PC

Benign

-0.85

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.75

M_CAP

Benign

0.046

MetaRNN

Benign

0.12

MetaSVM

Benign

-0.73

MutationAssessor

Benign

1.3

PhyloP100

0.59

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.62

REVEL

Uncertain

0.51

Sift

Benign

0.31

Sift4G

Benign

0.28

Polyphen

0.0030

Vest4

0.29

MVP

0.87

MPC

1.1

ClinPred

0.029

GERP RS

2.0

Varity_R

0.097

gMVP

0.76

Mutation Taster

=88/12

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over