5-180792009-G-T

Position:

• chr5-180792009-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002406.4(MGAT1):​c.963C>A​(p.His321Gln) 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. 16/21 in silico tools predict a benign outcome for this variant. 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: -0.584

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.097228944).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MGAT1	NM_002406.4	c.963C>A	p.His321Gln	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.963C>A	p.His321Gln	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

May 31, 2024

The c.963C>A (p.H321Q) alteration is located in exon 3 (coding exon 1) of the MGAT1 gene. This alteration results from a C to A substitution at nucleotide position 963, causing the histidine (H) at amino acid position 321 to be replaced by a glutamine (Q). 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	0.25
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	1.9
DANN	Benign	0.82
DEOGEN2	Benign	0.27	T;T;T;T;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.82	.;.;.;T;.
M_CAP	Benign	0.039	D
MetaRNN	Benign	0.097	T;T;T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-0.59	N;N;N;N;N
PrimateAI	Benign	0.46	T
PROVEAN	Benign	0.34	N;N;N;N;N
REVEL	Benign	0.27
Sift	Benign	0.53	T;T;T;T;T
Sift4G	Benign	0.37	T;T;T;T;T
Polyphen		0.0	B;B;B;B;B
Vest4		0.098
MutPred		0.35		Gain of MoRF binding (P = 0.0981);Gain of MoRF binding (P = 0.0981);Gain of MoRF binding (P = 0.0981);Gain of MoRF binding (P = 0.0981);Gain of MoRF binding (P = 0.0981);
MVP		0.31
MPC		0.79
ClinPred		0.094	T
GERP RS		-4.1
Varity_R		0.031
gMVP		0.66

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: chr5-180219009;