5-179798424-G-A

Position:

• chr5-179798424-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014275.5(MGAT4B):​c.1433C>T​(p.Ser478Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: MGAT4B NM_014275.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.05

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]

MGAT4B (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17421836).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MGAT4B	NM_014275.5	c.1433C>T	p.Ser478Leu	missense_variant	13/15	ENST00000292591.12	NP_055090.1
MGAT4B	NM_054013.3	c.1478C>T	p.Ser493Leu	missense_variant	12/14		NP_463459.1
MGAT4B	XM_024454349.2	c.998C>T	p.Ser333Leu	missense_variant	13/15		XP_024310117.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MGAT4B	ENST00000292591.12	c.1433C>T	p.Ser478Leu	missense_variant	13/15	1	NM_014275.5	ENSP00000292591.7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 04, 2024

The c.1478C>T (p.S493L) alteration is located in exon 12 (coding exon 12) of the MGAT4B gene. This alteration results from a C to T substitution at nucleotide position 1478, causing the serine (S) at amino acid position 493 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.047	.;T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.080
FATHMM_MKL	Uncertain	0.96	D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.17	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.88	.;L
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-1.2	N;N
REVEL	Benign	0.051
Sift	Benign	0.74	T;T
Sift4G	Benign	0.43	T;T
Polyphen		0.0	.;B
Vest4		0.48
MutPred		0.28		.;Loss of disorder (P = 0.034);
MVP		0.13
MPC		0.44
ClinPred		0.70	D
GERP RS		4.1
Varity_R		0.070
gMVP		0.47

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-179225424;