rs202004832

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_021996.6(GBGT1):ā€‹c.1001G>Cā€‹(p.Arg334Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000189 in 1,589,544 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: š‘“ 0.000013 ( 0 hom., cov: 32)
Exomes š‘“: 7.0e-7 ( 0 hom. )

Consequence

GBGT1
NM_021996.6 missense

Scores

8
6
4

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.62
Variant links:
Genes affected
GBGT1 (HGNC:20460): (globoside alpha-1,3-N-acetylgalactosaminyltransferase 1 (FORS blood group)) This gene encodes a glycosyltransferase that plays a role in the synthesis of Forssman glycolipid (FG), a member of the globoseries glycolipid family. Glycolipids such as FG form attachment sites for the binding of pathogens to cells; expression of this protein may determine host tropism to microorganisms. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2013]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.841

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GBGT1NM_021996.6 linkc.1001G>C p.Arg334Pro missense_variant Exon 7 of 7 ENST00000372040.9 NP_068836.2 Q8N5D6-1J7Q0Z1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GBGT1ENST00000372040.9 linkc.1001G>C p.Arg334Pro missense_variant Exon 7 of 7 1 NM_021996.6 ENSP00000361110.3 Q8N5D6-1
ENSG00000285245ENST00000647146.1 linkc.396+1558G>C intron_variant Intron 6 of 22 ENSP00000493691.1 A0A2R8Y471

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152198
Hom.:
0
Cov.:
32
show subpopulations
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000430
AC:
1
AN:
232566
Hom.:
0
AF XY:
0.00000798
AC XY:
1
AN XY:
125360
show subpopulations
Gnomad AFR exome
AF:
0.0000623
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.96e-7
AC:
1
AN:
1437346
Hom.:
0
Cov.:
31
AF XY:
0.00000140
AC XY:
1
AN XY:
712782
show subpopulations
Gnomad4 AFR exome
AF:
0.0000306
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152198
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74346
show subpopulations
Gnomad4 AFR
AF:
0.0000483
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.60
BayesDel_addAF
Uncertain
0.11
D
BayesDel_noAF
Uncertain
0.11
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Benign
0.24
T;.
Eigen
Pathogenic
0.82
Eigen_PC
Pathogenic
0.75
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.86
D;D
M_CAP
Benign
0.042
D
MetaRNN
Pathogenic
0.84
D;D
MetaSVM
Benign
-1.2
T
MutationAssessor
Pathogenic
3.5
H;.
PROVEAN
Pathogenic
-6.2
D;D
REVEL
Uncertain
0.47
Sift
Pathogenic
0.0
D;D
Sift4G
Pathogenic
0.0010
D;D
Polyphen
1.0
D;.
Vest4
0.87
MutPred
0.60
Loss of MoRF binding (P = 0.0285);.;
MVP
0.46
MPC
0.57
ClinPred
0.99
D
GERP RS
5.2
Varity_R
0.96
gMVP
0.86

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs202004832; hg19: chr9-136029007; API