12-85979490-A-T

Variant names:

• chr12-85979490-A-T
• NM_001351288.2:c.1236T>A

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.1236T>A​(p.Asp412Glu) 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. 16/22 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: 0.892
• 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=0.080367565).

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.1236T>A	p.Asp412Glu	missense	Exon 5 of 5	NP_001338217.1	Q9UBM8-1
	MGAT4C	NM_001351282.2		c.1350T>A	p.Asp450Glu	missense	Exon 6 of 6	NP_001338211.1
	MGAT4C	NM_001351283.2		c.1323T>A	p.Asp441Glu	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.1236T>A	p.Asp412Glu	missense	Exon 5 of 5	ENSP00000481096.1	Q9UBM8-1
	MGAT4C	ENST00000621808.5	TSL:1	c.1236T>A	p.Asp412Glu	missense	Exon 9 of 9	ENSP00000478300.1	Q9UBM8-1
	MGAT4C	ENST00000548651.6	TSL:5	c.1236T>A	p.Asp412Glu	missense	Exon 8 of 8	ENSP00000447253.1	Q9UBM8-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	4.7
DANN	Benign	0.21
DEOGEN2	Benign	0.14	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.69	D
M_CAP	Benign	0.0066	T
MetaRNN	Benign	0.080	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-1.7	N
PhyloP100		0.89
PrimateAI	Benign	0.42	T
PROVEAN	Benign	2.2	N
REVEL	Benign	0.049
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.027
MVP		0.072
ClinPred		0.055	T
GERP RS		3.1
Varity_R		0.039
gMVP		0.23
Mutation Taster		=85/15	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

hg19: chr12-86373268;