12-85989418-AA-GG

Variant names:

• chr12-85989418-AA-GG
• NM_001351288.2:c.128_129delTTinsCC
• MGAT4C p.Ile43Thr

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_001351288.2(MGAT4C):​c.128_129delTTinsCC​(p.Ile43Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MGAT4C NM_001351288.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.58
• 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 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

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.128_129delTTinsCC	p.Ile43Thr	missense	N/A	NP_001338217.1	Q9UBM8-1
	MGAT4C	NM_001351282.2		c.242_243delTTinsCC	p.Ile81Thr	missense	N/A	NP_001338211.1
	MGAT4C	NM_001351283.2		c.215_216delTTinsCC	p.Ile72Thr	missense	N/A	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.128_129delTTinsCC	p.Ile43Thr	missense	N/A	ENSP00000481096.1	Q9UBM8-1
	MGAT4C	ENST00000621808.5	TSL:1	c.128_129delTTinsCC	p.Ile43Thr	missense	N/A	ENSP00000478300.1	Q9UBM8-1
	MGAT4C	ENST00000547225.5	TSL:1	c.128_129delTTinsCC	p.Ile43Thr	missense	N/A	ENSP00000449172.1	F8VWY2

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		8.6

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr12-86383196;