rs144433730

Variant names:

• chr5-180791839-C-A
• rs144433730
• NM_002406.4:c.1133G>T

Your query was ambiguous. Multiple possible variants found:

• chr5-180791839-C-A
• chr5-180791839-C-G
• chr5-180791839-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_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. 17/22 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: not found (cov: 33)
• Consequence: MGAT1 NM_002406.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.592
• Publications: 0 publications found

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]

ACMG classification

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

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

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MGAT1	NM_002406.4	MANE Select	c.1133G>T	p.Arg378Leu	missense	Exon 2 of 2	NP_002397.2	P26572
	MGAT1	NM_001114617.2		c.1133G>T	p.Arg378Leu	missense	Exon 3 of 3	NP_001108089.1	P26572
	MGAT1	NM_001114618.1		c.1133G>T	p.Arg378Leu	missense	Exon 3 of 3	NP_001108090.1	P26572

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MGAT1	ENST00000307826.5	TSL:1 MANE Select	c.1133G>T	p.Arg378Leu	missense	Exon 2 of 2	ENSP00000311888.4	P26572
	MGAT1	ENST00000333055.8	TSL:2	c.1133G>T	p.Arg378Leu	missense	Exon 3 of 3	ENSP00000332073.3	P26572
	MGAT1	ENST00000393340.7	TSL:2	c.1133G>T	p.Arg378Leu	missense	Exon 3 of 3	ENSP00000377010.3	P26572

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
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
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.39	N
PhyloP100		0.59
PrimateAI	Benign	0.42	T
PROVEAN	Benign	1.1	N
REVEL	Benign	0.19
Sift	Benign	0.46	T
Sift4G	Benign	0.73	T
Polyphen		0.0	B
Vest4		0.091
MutPred		0.35		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
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs144433730; hg19: chr5-180218839;