NM_003779.4:c.1117C>T

Variant names:

Variant summary

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

The NM_003779.4(B4GALT3):c.1117C>T(p.Arg373Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000465 in 1,614,166 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 1 hom., cov: 32)

Exomes 𝑓: 0.000047 ( 1 hom. )

Consequence

B4GALT3
NM_003779.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.00

Publications

0 publications found

Variant links:

Genes affected

B4GALT3 (HGNC:926): (beta-1,4-galactosyltransferase 3) This gene is one of seven beta-1,4-galactosyltransferase (beta4GalT) genes. They encode type II membrane-bound glycoproteins that appear to have exclusive specificity for the donor substrate UDP-galactose; all transfer galactose in a beta1,4 linkage to similar acceptor sugars: GlcNAc, Glc, and Xyl. Each beta4GalT has a distinct function in the biosynthesis of different glycoconjugates and saccharide structures. As type II membrane proteins, they have an N-terminal hydrophobic signal sequence that directs the protein to the Golgi apparatus and which then remains uncleaved to function as a transmembrane anchor. By sequence similarity, the beta4GalTs form four groups: beta4GalT1 and beta4GalT2, beta4GalT3 and beta4GalT4, beta4GalT5 and beta4GalT6, and beta4GalT7. This gene encodes an enzyme that may be mainly involved in the synthesis of the first N-acetyllactosamine unit of poly-N-acetyllactosamine chains. Multiple alternatively spliced transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Dec 2010]

B4GALT3 links:

PPOX (HGNC:9280): (protoporphyrinogen oxidase) This gene encodes the penultimate enzyme of heme biosynthesis, which catalyzes the 6-electron oxidation of protoporphyrinogen IX to form protoporphyrin IX. Mutations in this gene cause variegate porphyria, an autosomal dominant disorder of heme metabolism resulting from a deficiency in protoporphyrinogen oxidase, an enzyme located on the inner mitochondrial membrane. Alternatively spliced transcript variants encoding the same protein have been identified. [provided by RefSeq, Jul 2008]

PPOX Gene-Disease associations (from GenCC):

variegate porphyria
Inheritance: AD, SD, AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Orphanet, Ambry Genetics, ClinGen

PPOX links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.2071599).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003779.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
B4GALT3	NM_003779.4	MANE Select	c.1117C>T	p.Arg373Trp	missense	Exon 8 of 8	NP_003770.1	O60512-1
B4GALT3	NM_001199873.1		c.1117C>T	p.Arg373Trp	missense	Exon 8 of 8	NP_001186802.1	O60512-1
B4GALT3	NM_001199874.1		c.1117C>T	p.Arg373Trp	missense	Exon 8 of 8	NP_001186803.1	A0A384NY44

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
B4GALT3	ENST00000319769.10	TSL:1 MANE Select	c.1117C>T	p.Arg373Trp	missense	Exon 8 of 8	ENSP00000320965.5	O60512-1
B4GALT3	ENST00000367998.5	TSL:1	c.1117C>T	p.Arg373Trp	missense	Exon 8 of 8	ENSP00000356977.1	O60512-1
B4GALT3	ENST00000622395.4	TSL:1	c.1117C>T	p.Arg373Trp	missense	Exon 8 of 8	ENSP00000480428.1	O60512-1

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.00633

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.0000875

AC:

AN:

251454

AF XY:

0.000125

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000578

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000472

AC:

AN:

1461882

Hom.:

Cov.:

AF XY:

0.0000619

AC XY:

AN XY:

727238

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.0000447

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.000301

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.00156

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000270

AC:

AN:

1112008

Other (OTH)

AF:

0.0000166

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152284

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74470

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41556

American (AMR)

AF:

0.00

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68012

Other (OTH)

AF:

0.000473

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000761

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.000107

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000119

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.32

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.019

Eigen

Uncertain

0.27

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.032

MetaRNN

Benign

0.21

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.69

PhyloP100

2.0

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-0.61

REVEL

Benign

0.13

Sift

Uncertain

0.0090

Sift4G

Uncertain

0.0090

Polyphen

0.98

Vest4

0.22

MVP

0.76

MPC

0.48

ClinPred

0.092

GERP RS

4.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.081

gMVP

0.64

Mutation Taster

=77/23

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over