Genetic Variant NM_021996.6:c.363C>T (chr9-133154258-G-A) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 0P and 3B. BP4_ModerateBP7

The NM_021996.6(GBGT1):c.363C>T(p.Tyr121Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000139 in 1,368,076 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

GBGT1
NM_021996.6 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.733

Publications

28 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.106027484).

BP7

Synonymous conserved (PhyloP=0.733 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GBGT1	NM_021996.6 link	c.363C>T	p.Tyr121Tyr	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
GBGT1	ENST00000372040.9 link	c.363C>T	p.Tyr121Tyr	synonymous_variant	Exon 7 of 7	1	NM_021996.6	ENSP00000361110.3		Q8N5D6-1
ENSG00000285245	ENST00000647146.1 link	c.396+920C>T		intron_variant	Intron 6 of 22			ENSP00000493691.1		A0A2R8Y471

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000431

AC:

AN:

185574

AF XY:

0.0000102

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000228

GnomAD4 exome

AF:

0.0000139

AC:

AN:

1368076

Hom.:

Cov.:

AF XY:

0.0000105

AC XY:

AN XY:

669520

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30962

American (AMR)

AF:

0.00

AC:

AN:

34344

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20746

East Asian (EAS)

AF:

0.00

AC:

AN:

38690

South Asian (SAS)

AF:

0.000232

AC:

AN:

73200

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47502

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5326

European-Non Finnish (NFE)

AF:

9.43e-7

AC:

AN:

1060922

Other (OTH)

AF:

0.0000177

AC:

AN:

56384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

1058

Bravo

AF:

0.00000378

ExAC

AF:

0.00000854

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.35

CADD

Benign

1.8

(source)

DANN

Benign

0.75

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.22

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.31

T;T

M_CAP

Benign

0.0043

MetaRNN

Benign

0.11

T;T

MetaSVM

Benign

-1.1

PhyloP100

0.73

PROVEAN

Benign

0.24

.;N

REVEL

Benign

0.0070

Sift

Benign

0.090

.;T

Vest4

0.41

MutPred

0.30

Gain of sheet (P = 0.0149);Gain of sheet (P = 0.0149);

MVP

0.21

ClinPred

0.039

GERP RS

1.5

Mutation Taster

=96/4

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over