chr12-85980280-C-G

Variant names:

• chr12-85980280-C-G
• rs748796788
• NM_001351288.2:c.446G>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001351288.2(MGAT4C):​c.446G>C​(p.Arg149Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. R149C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MGAT4C NM_001351288.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.13
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001351288.2. 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
	MGAT4C	NM_001351288.2	MANE Select	c.446G>C	p.Arg149Pro	missense	Exon 5 of 5	NP_001338217.1	Q9UBM8-1
	MGAT4C	NM_001351282.2		c.560G>C	p.Arg187Pro	missense	Exon 6 of 6	NP_001338211.1
	MGAT4C	NM_001351283.2		c.533G>C	p.Arg178Pro	missense	Exon 6 of 6	NP_001338212.1	Q9UBM8-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MGAT4C	ENST00000611864.5	TSL:5 MANE Select	c.446G>C	p.Arg149Pro	missense	Exon 5 of 5	ENSP00000481096.1	Q9UBM8-1
	MGAT4C	ENST00000621808.5	TSL:1	c.446G>C	p.Arg149Pro	missense	Exon 9 of 9	ENSP00000478300.1	Q9UBM8-1
	MGAT4C	ENST00000547225.5	TSL:1	c.446G>C	p.Arg149Pro	missense	Exon 6 of 6	ENSP00000449172.1	F8VWY2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.90
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.26	T
Eigen	Benign	0.061
Eigen_PC	Benign	0.026
FATHMM_MKL	Uncertain	0.97	D
M_CAP	Uncertain	0.17	D
MetaRNN	Uncertain	0.69	D
MetaSVM	Uncertain	-0.015	T
MutationAssessor	Benign	1.4	L
PhyloP100		6.1
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-2.6	D
REVEL	Uncertain	0.63
Sift	Benign	0.14	T
Sift4G	Benign	0.22	T
Polyphen		0.97	D
Vest4		0.46
MVP		0.58
ClinPred		0.96	D
GERP RS		2.6
Varity_R		0.71
gMVP		0.83
Mutation Taster		=76/24	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: rs748796788; hg19: chr12-86374058;