Genetic Variant GBGT1:p.Tyr121* (chr9-133154258-G-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_021996.6(GBGT1):c.363C>A(p.Tyr121*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0647 in 1,519,242 control chromosomes in the GnomAD database, including 3,502 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.060 ( 323 hom., cov: 32)

Exomes 𝑓: 0.065 ( 3179 hom. )

Consequence

GBGT1
NM_021996.6 stop_gained

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.733

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]

GBGT1 links:

ENSG00000285245 (HGNC:):

ENSG00000285245 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0705 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GBGT1	NM_021996.6 link	c.363C>A	p.Tyr121*	stop_gained	Exon 7 of 7	ENST00000372040.9	NP_068836.2	Q8N5D6-1J7Q0Z1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GBGT1	ENST00000372040.9 link	c.363C>A	p.Tyr121*	stop_gained	Exon 7 of 7	1	NM_021996.6	ENSP00000361110.3		Q8N5D6-1
ENSG00000285245	ENST00000647146.1 link	c.396+920C>A		intron_variant	Intron 6 of 22			ENSP00000493691.1		A0A2R8Y471

Frequencies

GnomAD3 genomes

AF:

0.0598

AC:

9100

AN:

152138

Hom.:

320

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0409

Gnomad AMI

AF:

0.0570

Gnomad AMR

AF:

0.0432

Gnomad ASJ

AF:

0.0813

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.0548

Gnomad FIN

AF:

0.101

Gnomad MID

AF:

0.0854

Gnomad NFE

AF:

0.0722

Gnomad OTH

AF:

0.0650

GnomAD2 exomes

AF:

0.0578

AC:

10722

AN:

185574

AF XY:

0.0598

show subpopulations

Gnomad AFR exome

AF:

0.0412

Gnomad AMR exome

AF:

0.0334

Gnomad ASJ exome

AF:

0.0872

Gnomad EAS exome

AF:

0.000180

Gnomad FIN exome

AF:

0.105

Gnomad NFE exome

AF:

0.0706

Gnomad OTH exome

AF:

0.0621

GnomAD4 exome

AF:

0.0653

AC:

89199

AN:

1366986

Hom.:

3179

Cov.:

AF XY:

0.0657

AC XY:

43960

AN XY:

669032

show subpopulations

Gnomad4 AFR exome

AF:

0.0432

AC:

1337

AN:

30944

Gnomad4 AMR exome

AF:

0.0336

AC:

1153

AN:

34338

Gnomad4 ASJ exome

AF:

0.0856

AC:

1776

AN:

20742

Gnomad4 EAS exome

AF:

0.000181

AC:

AN:

38688

Gnomad4 SAS exome

AF:

0.0551

AC:

4030

AN:

73172

Gnomad4 FIN exome

AF:

0.100

AC:

4766

AN:

47458

Gnomad4 NFE exome

AF:

0.0681

AC:

72152

AN:

1059982

Gnomad4 Remaining exome

AF:

0.0603

AC:

3399

AN:

56338

Heterozygous variant carriers

3610

7220

10829

14439

18049

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

2732

5464

8196

10928

13660

<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:

0.0598

AC:

9106

AN:

152256

Hom.:

323

Cov.:

AF XY:

0.0605

AC XY:

4501

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.0409

AC:

0.0408748

AN:

0.0408748

Gnomad4 AMR

AF:

0.0431

AC:

0.0431429

AN:

0.0431429

Gnomad4 ASJ

AF:

0.0813

AC:

0.081268

AN:

0.081268

Gnomad4 EAS

AF:

0.000580

AC:

0.000579822

AN:

0.000579822

Gnomad4 SAS

AF:

0.0559

AC:

0.0559006

AN:

0.0559006

Gnomad4 FIN

AF:

0.101

AC:

0.100793

AN:

0.100793

Gnomad4 NFE

AF:

0.0722

AC:

0.0722038

AN:

0.0722038

Gnomad4 OTH

AF:

0.0639

AC:

0.06386

AN:

0.06386

Heterozygous variant carriers

450

901

1351

1802

2252

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

120

240

360

480

600

<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:

0.0647

Hom.:

1058

Bravo

AF:

0.0538

TwinsUK

AF:

0.0628

AC:

233

ALSPAC

AF:

0.0669

AC:

258

ESP6500AA

AF:

0.0452

AC:

199

ESP6500EA

AF:

0.0731

AC:

629

ExAC

AF:

0.0572

AC:

6693

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.37

CADD

Pathogenic

DANN

Uncertain

0.99

Eigen

Uncertain

0.34

Eigen_PC

Benign

0.11

FATHMM_MKL

Benign

0.72

LIST_S2

Benign

0.26

T;T

MetaRNN

Benign

0.0018

T;T

MetaSVM

Benign

-1.1

PROVEAN

Benign

0.62

.;N

REVEL

Benign

0.015

Sift

Benign

0.60

.;T

Vest4

0.38

ClinPred

0.094

GERP RS

1.5

Mutation Taster

=178/22

polymorphism (auto)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over