2-98678362-C-G

Variant summary

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

The NM_012214.3(MGAT4A):c.204G>C(p.Gln68His) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: MGAT4A NM_012214.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.762

Genes affected

MGAT4A (HGNC:7047): (alpha-1,3-mannosyl-glycoprotein 4-beta-N-acetylglucosaminyltransferase A) This gene encodes a key glycosyltransferase that regulates the formation of tri- and multiantennary branching structures in the Golgi apparatus. The encoded protein, in addition to the related isoenzyme B, catalyzes the transfer of N-acetylglucosamine (GlcNAc) from UDP-GlcNAc in a beta-1,4 linkage to the Man-alpha-1,3-Man-beta-1,4-GlcNAc arm of R-Man-alpha-1,6(GlcNAc-beta-1,2-Man-alpha-1,3)Man-beta-1,4-GlcNAc-beta-1,4-GlcNAc-beta-1-Asn. The encoded protein may play a role in regulating the availability of serum glycoproteins, oncogenesis, and differentiation. [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=0.09726223).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MGAT4A	NM_012214.3	c.204G>C	p.Gln68His	missense_variant	3/16	ENST00000393487.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MGAT4A	ENST00000393487.6	c.204G>C	p.Gln68His	missense_variant	3/16	5	NM_012214.3	P1
MGAT4A	ENST00000264968.7	c.204G>C	p.Gln68His	missense_variant	2/15	1		P1
MGAT4A	ENST00000409391.1	c.204G>C	p.Gln68His	missense_variant	3/16	5		P1
MGAT4A	ENST00000484936.5	n.467G>C		non_coding_transcript_exon_variant	3/5	5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

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

Nov 18, 2022

The c.204G>C (p.Q68H) alteration is located in exon 3 (coding exon 2) of the MGAT4A gene. This alteration results from a G to C substitution at nucleotide position 204, causing the glutamine (Q) at amino acid position 68 to be replaced by a histidine (H). 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	0.15
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
Cadd	Benign	17
Dann	Benign	0.97
DEOGEN2	Benign	0.054	T;T;T
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.27
FATHMM_MKL	Uncertain	0.83	D
M_CAP	Benign	0.0076	T
MetaRNN	Benign	0.097	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L;L;L
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.94	N;N;N
REVEL	Benign	0.074
Sift	Benign	0.23	T;T;T
Sift4G	Benign	0.33	T;T;T
Polyphen		0.0030	B;B;B
Vest4		0.39
MutPred		0.40		Loss of disorder (P = 0.092);Loss of disorder (P = 0.092);Loss of disorder (P = 0.092);
MVP		0.34
MPC		0.32
ClinPred		0.26	T
GERP RS		1.1
Varity_R		0.078
gMVP		0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr2-99294825;