rs752137181

Variant names:

• chr5-179799093-C-G
• rs752137181
• NM_014275.5:c.1178G>C

Your query was ambiguous. Multiple possible variants found:

• chr5-179799093-C-G
• chr5-179799093-C-T

Variant summary

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

The NM_014275.5(MGAT4B):​c.1178G>C​(p.Arg393Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. R393W) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MGAT4B NM_014275.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.05
• Publications: 0 publications found

Genes affected

MGAT4B (HGNC:7048): (alpha-1,3-mannosyl-glycoprotein 4-beta-N-acetylglucosaminyltransferase B) This gene encodes a key glycosyltransferase that regulates the formation of tri- and multiantennary branching structures in the Golgi apparatus. The encoded protein, in addition to the related isoenzyme A, catalyzes the transfer of N-acetylglucosamine (GlcNAc) from UDP-GlcNAc in a beta-1,4 linkage to the Man-alpha-1,3-Man-beta-1,4-GlcNAc arm of R-Man-alpha-1,6(GlcNAc-beta-1,2-Man-alpha-1,3)Man-beta-1,4-GlcNAc-beta-1,4-GlcNAc-beta-1-Asn. The encoded protein may play a role in regulating the availability of serum glycoproteins, oncogenesis, and differentiation. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MGAT4B	NM_014275.5	c.1178G>C	p.Arg393Pro	missense_variant	Exon 11 of 15	ENST00000292591.12	NP_055090.1
MGAT4B	NM_054013.3	c.1223G>C	p.Arg408Pro	missense_variant	Exon 10 of 14		NP_463459.1
MGAT4B	XM_024454349.2	c.743G>C	p.Arg248Pro	missense_variant	Exon 11 of 15		XP_024310117.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MGAT4B	ENST00000292591.12	c.1178G>C	p.Arg393Pro	missense_variant	Exon 11 of 15	1	NM_014275.5	ENSP00000292591.7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.78
BayesDel_addAF	Uncertain	0.039	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.087	.;T
Eigen	Benign	0.12
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.95	D
M_CAP	Benign	0.016	T
MetaRNN	Uncertain	0.51	D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	.;L
PhyloP100		3.0
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-2.0	N;N
REVEL	Benign	0.10
Sift	Benign	0.12	T;T
Sift4G	Benign	0.14	T;T
Polyphen		0.63	.;P
Vest4		0.64
MutPred		0.41		.;Loss of MoRF binding (P = 0.0094);
MVP		0.25
MPC		1.3
ClinPred		0.88	D
GERP RS		3.3
Varity_R		0.45
gMVP		0.71
Mutation Taster		=75/25	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: rs752137181; hg19: chr5-179226093;