rs200641508

Variant names:

• chr12-85989419-A-G
• rs200641508
• NM_001351288.2:c.128T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001351288.2(MGAT4C):​c.128T>C​(p.Ile43Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000363 in 1,604,124 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00039 (0 hom.)
• Consequence: MGAT4C NM_001351288.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.58
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.19420469).

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.128T>C	p.Ile43Thr	missense	Exon 3 of 5	NP_001338217.1	Q9UBM8-1
	MGAT4C	NM_001351282.2		c.242T>C	p.Ile81Thr	missense	Exon 4 of 6	NP_001338211.1
	MGAT4C	NM_001351283.2		c.215T>C	p.Ile72Thr	missense	Exon 4 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.128T>C	p.Ile43Thr	missense	Exon 3 of 5	ENSP00000481096.1	Q9UBM8-1
	MGAT4C	ENST00000621808.5	TSL:1	c.128T>C	p.Ile43Thr	missense	Exon 7 of 9	ENSP00000478300.1	Q9UBM8-1
	MGAT4C	ENST00000547225.5	TSL:1	c.128T>C	p.Ile43Thr	missense	Exon 4 of 6	ENSP00000449172.1	F8VWY2

Frequencies

GnomAD3 genomes AF: 0.000112 AC: 17 AN: 152070 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000482

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: 0.000221

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000127 AC: 31 AN: 243946 AF XY: 0.000144

Gnomad AFR exome AF: 0.000125

Gnomad AMR exome AF: 0.0000310

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000242

Gnomad OTH exome AF: 0.000169

GnomAD4 exome AF: 0.000389 AC: 565 AN: 1452054 Hom.: 0 Cov.: 30 AF XY: 0.000400 AC XY: 289 AN XY: 721988

African (AFR) AF: 0.0000604 AC: 2 AN: 33116

American (AMR) AF: 0.0000232 AC: 1 AN: 43176

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25830

East Asian (EAS) AF: 0.00 AC: 0 AN: 39346

South Asian (SAS) AF: 0.00 AC: 0 AN: 83558

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53264

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5718

European-Non Finnish (NFE) AF: 0.000491 AC: 544 AN: 1108066

Other (OTH) AF: 0.000300 AC: 18 AN: 59980

GnomAD4 genome AF: 0.000112 AC: 17 AN: 152070 Hom.: 0 Cov.: 32 AF XY: 0.000162 AC XY: 12 AN XY: 74268

African (AFR) AF: 0.0000482 AC: 2 AN: 41464

American (AMR) AF: 0.00 AC: 0 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

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

European-Non Finnish (NFE) AF: 0.000221 AC: 15 AN: 67910

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.000133 Hom.: 0

Bravo AF: 0.000144

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.000107 AC: 13

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	0.073
BayesDel_addAF	Benign	-0.018	T
BayesDel_noAF	Uncertain	0.030
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Pathogenic	0.99	D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PhyloP100		8.6
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	0.26	N
REVEL	Benign	0.20
Sift	Benign	0.62	T
Sift4G	Benign	0.62	T
Polyphen		0.73	P
Vest4		0.62
MVP		0.21
ClinPred		0.10	T
GERP RS		5.8
Varity_R		0.15
gMVP		0.59
Mutation Taster		=27/73	disease causing

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: rs200641508; hg19: chr12-86383197;