12-85979395-C-A

Variant names:

• chr12-85979395-C-A
• rs1287774088
• NM_001351288.2:c.1331G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001351288.2(MGAT4C):​c.1331G>T​(p.Gly444Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,460,976 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. 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. G444D) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: MGAT4C NM_001351288.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.26
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.090308994).

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.1331G>T	p.Gly444Val	missense	Exon 5 of 5	NP_001338217.1	Q9UBM8-1
	MGAT4C	NM_001351282.2		c.1445G>T	p.Gly482Val	missense	Exon 6 of 6	NP_001338211.1
	MGAT4C	NM_001351283.2		c.1418G>T	p.Gly473Val	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.1331G>T	p.Gly444Val	missense	Exon 5 of 5	ENSP00000481096.1	Q9UBM8-1
	MGAT4C	ENST00000621808.5	TSL:1	c.1331G>T	p.Gly444Val	missense	Exon 9 of 9	ENSP00000478300.1	Q9UBM8-1
	MGAT4C	ENST00000548651.6	TSL:5	c.1331G>T	p.Gly444Val	missense	Exon 8 of 8	ENSP00000447253.1	Q9UBM8-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250576 AF XY: 0.00000738

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000291

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1460976 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726814

African (AFR) AF: 0.00 AC: 0 AN: 33448

American (AMR) AF: 0.0000224 AC: 1 AN: 44610

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26114

East Asian (EAS) AF: 0.00 AC: 0 AN: 39652

South Asian (SAS) AF: 0.00 AC: 0 AN: 86222

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53364

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111466

Other (OTH) AF: 0.00 AC: 0 AN: 60342

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	18
DANN	Benign	0.80
DEOGEN2	Benign	0.083	T
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.28
FATHMM_MKL	Uncertain	0.89	D
M_CAP	Benign	0.0076	T
MetaRNN	Benign	0.090	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.26	N
PhyloP100		4.3
PrimateAI	Benign	0.22	T
PROVEAN	Benign	0.36	N
REVEL	Benign	0.024
Sift	Benign	0.28	T
Sift4G	Benign	0.32	T
Polyphen		0.11	B
Vest4		0.12
MVP		0.14
ClinPred		0.082	T
GERP RS		3.3
Varity_R		0.063
gMVP		0.39
Mutation Taster		=68/32	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: rs1287774088; hg19: chr12-86373173;