chr9-133154257-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_021996.6(GBGT1):ā€‹c.364A>Gā€‹(p.Thr122Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000438 in 1,369,308 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000044 ( 0 hom. )

Consequence

GBGT1
NM_021996.6 missense

Scores

1
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.420
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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.16368482).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GBGT1NM_021996.6 linkuse as main transcriptc.364A>G p.Thr122Ala missense_variant 7/7 ENST00000372040.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GBGT1ENST00000372040.9 linkuse as main transcriptc.364A>G p.Thr122Ala missense_variant 7/71 NM_021996.6 P1Q8N5D6-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000108
AC:
2
AN:
185848
Hom.:
0
AF XY:
0.0000101
AC XY:
1
AN XY:
98610
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000602
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000116
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000438
AC:
6
AN:
1369308
Hom.:
0
Cov.:
28
AF XY:
0.00000597
AC XY:
4
AN XY:
670088
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000517
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000377
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsMay 03, 2023The c.364A>G (p.T122A) alteration is located in exon 7 (coding exon 6) of the GBGT1 gene. This alteration results from a A to G substitution at nucleotide position 364, causing the threonine (T) at amino acid position 122 to be replaced by an alanine (A). 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
0.079
BayesDel_addAF
Benign
-0.20
T
BayesDel_noAF
Benign
-0.44
CADD
Benign
19
DANN
Uncertain
0.99
Eigen
Benign
0.095
Eigen_PC
Benign
0.084
FATHMM_MKL
Benign
0.73
D
LIST_S2
Benign
0.26
T;T
M_CAP
Benign
0.024
T
MetaRNN
Benign
0.16
T;T
MetaSVM
Benign
-0.66
T
MutationTaster
Benign
1.0
D;D;D;N;D
PROVEAN
Benign
-0.20
.;N
REVEL
Benign
0.092
Sift
Benign
0.17
.;T
Vest4
0.50
MutPred
0.20
Gain of MoRF binding (P = 0.057);Gain of MoRF binding (P = 0.057);
MVP
0.40
ClinPred
0.20
T
GERP RS
5.4

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: rs962912980; hg19: chr9-136029644; API