rs148327471

Variant names:

• chr5-179800545-G-A
• rs148327471
• NM_014275.5:c.658C>T

Your query was ambiguous. Multiple possible variants found:

• chr5-179800545-G-A
• chr5-179800545-G-C
• chr5-179800545-G-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.658C>T​(p.His220Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000323 in 1,611,846 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict 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. H220D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000034 (0 hom.)
• Consequence: MGAT4B NM_014275.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.90
• Publications: 4 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=0.26910388).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MGAT4B	NM_014275.5	c.658C>T	p.His220Tyr	missense_variant	Exon 6 of 15	ENST00000292591.12	NP_055090.1
MGAT4B	NM_054013.3	c.703C>T	p.His235Tyr	missense_variant	Exon 5 of 14		NP_463459.1
MGAT4B	XM_024454349.2	c.223C>T	p.His75Tyr	missense_variant	Exon 6 of 15		XP_024310117.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MGAT4B	ENST00000292591.12	c.658C>T	p.His220Tyr	missense_variant	Exon 6 of 15	1	NM_014275.5	ENSP00000292591.7

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152048 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000483

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

GnomAD2 exomes AF: 0.0000164 AC: 4 AN: 244058 AF XY: 0.0000150

Gnomad AFR exome AF: 0.0000659

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: 0.0000274

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000336 AC: 49 AN: 1459798 Hom.: 0 Cov.: 32 AF XY: 0.0000317 AC XY: 23 AN XY: 726126

African (AFR) AF: 0.0000598 AC: 2 AN: 33456

American (AMR) AF: 0.00 AC: 0 AN: 44550

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26074

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.00 AC: 0 AN: 86078

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52374

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5720

European-Non Finnish (NFE) AF: 0.0000405 AC: 45 AN: 1111540

Other (OTH) AF: 0.0000332 AC: 2 AN: 60318

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152048 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 74258

African (AFR) AF: 0.0000483 AC: 2 AN: 41400

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

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5156

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67992

Other (OTH) AF: 0.00 AC: 0 AN: 2084

Alfa AF: 0.00 Hom.: 3

Bravo AF: 0.0000113

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.11	.;T;.
Eigen	Benign	0.15
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.87	D
M_CAP	Benign	0.0073	T
MetaRNN	Benign	0.27	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	.;L;.
PhyloP100		1.9
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-1.9	N;N;N
REVEL	Benign	0.053
Sift	Benign	0.68	T;T;T
Sift4G	Benign	1.0	T;T;T
Polyphen		0.84, 0.0	.;P;B
Vest4		0.50
MutPred		0.34		.;Gain of phosphorylation at H220 (P = 0.0364);.;
MVP		0.11
MPC		0.59
ClinPred		0.094	T
GERP RS		4.8
PromoterAI		-0.0086	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.17
gMVP		0.55
Mutation Taster		=95/5	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: rs148327471; hg19: chr5-179227545;