12-85983664-C-G

Variant names:

• chr12-85983664-C-G
• rs149974845
• NM_001351288.2:c.154G>C

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.154G>C​(p.Asp52His) variant causes a missense change. The variant allele was found at a frequency of 0.00000191 in 1,569,030 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. D52N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: MGAT4C NM_001351288.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.72
• Publications: 1 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=0.23940277).

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.154G>C	p.Asp52His	missense	Exon 4 of 5	NP_001338217.1	Q9UBM8-1
	MGAT4C	NM_001351282.2		c.268G>C	p.Asp90His	missense	Exon 5 of 6	NP_001338211.1
	MGAT4C	NM_001351283.2		c.241G>C	p.Asp81His	missense	Exon 5 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.154G>C	p.Asp52His	missense	Exon 4 of 5	ENSP00000481096.1	Q9UBM8-1
	MGAT4C	ENST00000621808.5	TSL:1	c.154G>C	p.Asp52His	missense	Exon 8 of 9	ENSP00000478300.1	Q9UBM8-1
	MGAT4C	ENST00000547225.5	TSL:1	c.154G>C	p.Asp52His	missense	Exon 5 of 6	ENSP00000449172.1	F8VWY2

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152058 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000141 AC: 2 AN: 1416972 Hom.: 0 Cov.: 29 AF XY: 0.00000284 AC XY: 2 AN XY: 704400

African (AFR) AF: 0.00 AC: 0 AN: 31128

American (AMR) AF: 0.00 AC: 0 AN: 36026

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24548

East Asian (EAS) AF: 0.00 AC: 0 AN: 37912

South Asian (SAS) AF: 0.00 AC: 0 AN: 78124

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5620

European-Non Finnish (NFE) AF: 9.15e-7 AC: 1 AN: 1092490

Other (OTH) AF: 0.0000171 AC: 1 AN: 58518

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152058 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74288

African (AFR) AF: 0.00 AC: 0 AN: 41390

American (AMR) AF: 0.00 AC: 0 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68012

Other (OTH) AF: 0.00 AC: 0 AN: 2088

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.42
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.18	T
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.050
FATHMM_MKL	Pathogenic	0.98	D
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.6	L
PhyloP100		4.7
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-0.93	N
REVEL	Benign	0.090
Sift	Uncertain	0.015	D
Sift4G	Uncertain	0.012	D
Polyphen		0.92	P
Vest4		0.52
MVP		0.28
ClinPred		0.83	D
GERP RS		2.6
Varity_R		0.13
gMVP		0.62
Mutation Taster		=70/30	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs149974845; hg19: chr12-86377442;