5-179799009-C-A

Variant names:

• chr5-179799009-C-A
• rs748216524
• NM_014275.5:c.1262G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_014275.5(MGAT4B):​c.1262G>T​(p.Arg421Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000144 in 1,461,574 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. R421H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: MGAT4B NM_014275.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.00
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.42131975).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014275.5. 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
	MGAT4B	NM_014275.5	MANE Select	c.1262G>T	p.Arg421Leu	missense	Exon 11 of 15	NP_055090.1	Q9UQ53-1
	MGAT4B	NM_054013.3		c.1307G>T	p.Arg436Leu	missense	Exon 10 of 14	NP_463459.1	Q9UQ53-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MGAT4B	ENST00000292591.12	TSL:1 MANE Select	c.1262G>T	p.Arg421Leu	missense	Exon 11 of 15	ENSP00000292591.7	Q9UQ53-1
	MGAT4B	ENST00000518778.5	TSL:1	c.734G>T	p.Arg245Leu	missense	Exon 8 of 12	ENSP00000428906.1	H0YB84
	MGAT4B	ENST00000519836.5	TSL:1	c.864G>T	p.Ala288Ala	synonymous	Exon 8 of 12	ENSP00000430721.1	H0YC11

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251376 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000144 AC: 21 AN: 1461574 Hom.: 0 Cov.: 32 AF XY: 0.0000124 AC XY: 9 AN XY: 727086

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53110

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000171 AC: 19 AN: 1112006

Other (OTH) AF: 0.0000331 AC: 2 AN: 60392

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.68
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.16
FATHMM_MKL	Uncertain	0.94	D
M_CAP	Benign	0.0095	T
MetaRNN	Benign	0.42	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L
PhyloP100		5.0
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.088
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.0050	D
Polyphen		0.089	B
Vest4		0.60
MutPred		0.47		Loss of sheet (P = 0.0315)
MVP		0.12
MPC		0.62
ClinPred		0.86	D
GERP RS		2.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7
Varity_R		0.15
gMVP		0.59
Mutation Taster		=81/19	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: rs748216524; hg19: chr5-179226009;