12-85979681-T-C

Variant names:

• chr12-85979681-T-C
• rs1884314402
• NM_001351288.2:c.1045A>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001351288.2(MGAT4C):​c.1045A>G​(p.Met349Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MGAT4C NM_001351288.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.01

Genes affected

MGAT4C (HGNC:30871): (MGAT4 family member C) Predicted to enable acetylglucosaminyltransferase activity. Predicted to be involved in protein N-linked glycosylation. Predicted to be located in Golgi membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30381706).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MGAT4C	NM_001351288.2	c.1045A>G	p.Met349Val	missense_variant	Exon 5 of 5	ENST00000611864.5	NP_001338217.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MGAT4C	ENST00000611864.5	c.1045A>G	p.Met349Val	missense_variant	Exon 5 of 5	5	NM_001351288.2	ENSP00000481096.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000469 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 10, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1045A>G (p.M349V) alteration is located in exon 7 (coding exon 3) of the MGAT4C gene. This alteration results from a A to G substitution at nucleotide position 1045, causing the methionine (M) at amino acid position 349 to be replaced by a valine (V). 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	0.27
BayesDel_addAF	Benign	-0.033	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	21
DANN	Benign	0.87
DEOGEN2	Uncertain	0.43	T;T;T;T;T;.
Eigen	Benign	-0.078
Eigen_PC	Benign	0.025
FATHMM_MKL	Uncertain	0.94	D
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.30	T;T;T;T;T;T
MetaSVM	Benign	-0.87	T
MutationAssessor	Uncertain	2.4	M;M;M;M;M;.
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-1.9	.;.;N;.;N;N
REVEL	Benign	0.22
Sift	Uncertain	0.010	.;.;D;.;D;D
Sift4G	Uncertain	0.026	D;D;D;D;D;.
Polyphen		0.069	B;B;B;B;B;.
Vest4		0.37
MVP		0.37
ClinPred		0.76	D
GERP RS		4.9
Varity_R		0.54
gMVP		0.71

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

LitVar

Other links and lift over

dbSNP: rs1884314402; hg19: chr12-86373459;