5-180791731-G-C

Position:

• chr5-180791731-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_002406.4(MGAT1):​c.1241C>G​(p.Ala414Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: MGAT1 NM_002406.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.97

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MGAT1	NM_002406.4	c.1241C>G	p.Ala414Gly	missense_variant	2/2	ENST00000307826.5	NP_002397.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MGAT1	ENST00000307826.5	c.1241C>G	p.Ala414Gly	missense_variant	2/2	1	NM_002406.4	ENSP00000311888.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 14, 2023

The c.1241C>G (p.A414G) alteration is located in exon 3 (coding exon 1) of the MGAT1 gene. This alteration results from a C to G substitution at nucleotide position 1241, causing the alanine (A) at amino acid position 414 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Uncertain	0.077	D
BayesDel_noAF	Benign	-0.13
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.57	D;D;D;D;D
Eigen	Benign	0.083
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.90	.;.;.;D;.
M_CAP	Benign	0.060	D
MetaRNN	Uncertain	0.53	D;D;D;D;D
MetaSVM	Benign	-0.32	T
MutationAssessor	Benign	1.2	L;L;L;L;L
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-2.3	N;N;N;N;N
REVEL	Uncertain	0.54
Sift	Uncertain	0.0060	D;D;D;D;D
Sift4G	Uncertain	0.019	D;D;D;D;D
Polyphen		0.0040	B;B;B;B;B
Vest4		0.36
MutPred		0.85		Gain of relative solvent accessibility (P = 0.0479);Gain of relative solvent accessibility (P = 0.0479);Gain of relative solvent accessibility (P = 0.0479);Gain of relative solvent accessibility (P = 0.0479);Gain of relative solvent accessibility (P = 0.0479);
MVP		0.65
MPC		0.94
ClinPred		0.92	D
GERP RS		5.0
Varity_R		0.29
gMVP		0.52

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: chr5-180218731;