Genetic Variant MGAT1:p.Leu381Val (chr5-180791831-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002406.4(MGAT1):c.1141C>G(p.Leu381Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,876 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

MGAT1
NM_002406.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.39

Publications

17 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14903453).

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
MGAT1	NM_002406.4	MANE Select	c.1141C>G	p.Leu381Val	missense	Exon 2 of 2	NP_002397.2
MGAT1	NM_001114617.2		c.1141C>G	p.Leu381Val	missense	Exon 3 of 3	NP_001108089.1
MGAT1	NM_001114618.1		c.1141C>G	p.Leu381Val	missense	Exon 3 of 3	NP_001108090.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
MGAT1	ENST00000307826.5	TSL:1 MANE Select	c.1141C>G	p.Leu381Val	missense	Exon 2 of 2	ENSP00000311888.4
MGAT1	ENST00000333055.8	TSL:2	c.1141C>G	p.Leu381Val	missense	Exon 3 of 3	ENSP00000332073.3
MGAT1	ENST00000393340.7	TSL:2	c.1141C>G	p.Leu381Val	missense	Exon 3 of 3	ENSP00000377010.3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461876

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727240

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53412

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1112002

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.058

BayesDel_noAF

Benign

-0.32

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.32

Eigen

Benign

-0.15

Eigen_PC

Benign

-0.011

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.71

M_CAP

Benign

0.034

MetaRNN

Benign

0.15

MetaSVM

Benign

-0.43

MutationAssessor

Benign

1.8

PhyloP100

1.4

PrimateAI

Uncertain

0.48

PROVEAN

Benign

0.080

REVEL

Benign

0.15

Sift

Benign

0.41

Sift4G

Benign

0.44

Polyphen

0.090

Vest4

0.12

MutPred

0.30

Gain of methylation at K379 (P = 0.0638)

MVP

0.68

MPC

0.81

ClinPred

0.14

GERP RS

4.0

Varity_R

0.053

gMVP

0.31

Mutation Taster

=93/7

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.17

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