chr9-133153925-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001282629.2(GBGT1):​c.677C>T​(p.Thr226Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00494 in 1,609,570 control chromosomes in the GnomAD database, including 303 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.025 ( 163 hom., cov: 32)
Exomes 𝑓: 0.0028 ( 140 hom. )

Consequence

GBGT1
NM_001282629.2 missense

Scores

1
12

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.632
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 Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0016729832).
BP6
Variant 9-133153925-G-A is Benign according to our data. Variant chr9-133153925-G-A is described in ClinVar as [Benign]. Clinvar id is 775281.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0836 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GBGT1NM_021996.6 linkc.696C>T p.Tyr232Tyr synonymous_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.696C>T p.Tyr232Tyr synonymous_variant Exon 7 of 7 1 NM_021996.6 ENSP00000361110.3 Q8N5D6-1
ENSG00000285245ENST00000647146.1 linkc.396+1253C>T intron_variant Intron 6 of 22 ENSP00000493691.1 A0A2R8Y471

Frequencies

GnomAD3 genomes
AF:
0.0251
AC:
3821
AN:
152196
Hom.:
162
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0861
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0111
Gnomad ASJ
AF:
0.000864
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000620
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00633
Gnomad NFE
AF:
0.000573
Gnomad OTH
AF:
0.0182
GnomAD3 exomes
AF:
0.00685
AC:
1714
AN:
250390
Hom.:
59
AF XY:
0.00501
AC XY:
679
AN XY:
135406
show subpopulations
Gnomad AFR exome
AF:
0.0854
Gnomad AMR exome
AF:
0.00585
Gnomad ASJ exome
AF:
0.00170
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.000131
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000734
Gnomad OTH exome
AF:
0.00344
GnomAD4 exome
AF:
0.00283
AC:
4121
AN:
1457256
Hom.:
140
Cov.:
32
AF XY:
0.00244
AC XY:
1766
AN XY:
723940
show subpopulations
Gnomad4 AFR exome
AF:
0.0863
Gnomad4 AMR exome
AF:
0.00648
Gnomad4 ASJ exome
AF:
0.00196
Gnomad4 EAS exome
AF:
0.0000253
Gnomad4 SAS exome
AF:
0.000151
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000443
Gnomad4 OTH exome
AF:
0.00623
GnomAD4 genome
AF:
0.0251
AC:
3824
AN:
152314
Hom.:
163
Cov.:
32
AF XY:
0.0241
AC XY:
1793
AN XY:
74470
show subpopulations
Gnomad4 AFR
AF:
0.0859
Gnomad4 AMR
AF:
0.0111
Gnomad4 ASJ
AF:
0.000864
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000621
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000573
Gnomad4 OTH
AF:
0.0180
Alfa
AF:
0.00516
Hom.:
24
Bravo
AF:
0.0282
TwinsUK
AF:
0.000809
AC:
3
ALSPAC
AF:
0.000778
AC:
3
ESP6500AA
AF:
0.0826
AC:
364
ESP6500EA
AF:
0.00116
AC:
10
ExAC
AF:
0.00816
AC:
991
Asia WGS
AF:
0.00375
AC:
13
AN:
3478
EpiCase
AF:
0.000654
EpiControl
AF:
0.000534

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Apr 09, 2018
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

-
Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.47
T
BayesDel_noAF
Benign
-0.38
CADD
Benign
1.9
DANN
Benign
0.72
Eigen
Benign
-0.79
Eigen_PC
Benign
-0.96
FATHMM_MKL
Benign
0.10
N
LIST_S2
Benign
0.38
T
MetaRNN
Benign
0.0017
T
MetaSVM
Benign
-1.0
T
PROVEAN
Benign
1.3
N
REVEL
Benign
0.036
Sift
Pathogenic
0.0
D
Vest4
0.076
MVP
0.17
ClinPred
0.015
T
GERP RS
-2.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs34691037; hg19: chr9-136029312; API