9-133154188-A-G

Variant names:

• chr9-133154188-A-G
• rs776225870
• NM_021996.6:c.433T>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_021996.6(GBGT1):​c.433T>C​(p.Tyr145His) variant causes a missense change. The variant allele was found at a frequency of 0.0000007 in 1,428,880 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: GBGT1 NM_021996.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.94

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]

ENSG00000285245 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GBGT1	NM_021996.6	c.433T>C	p.Tyr145His	missense_variant	Exon 7 of 7	ENST00000372040.9	NP_068836.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GBGT1	ENST00000372040.9	c.433T>C	p.Tyr145His	missense_variant	Exon 7 of 7	1	NM_021996.6	ENSP00000361110.3
ENSG00000285245	ENST00000647146.1	c.396+990T>C		intron_variant	Intron 6 of 22			ENSP00000493691.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000425 AC: 1 AN: 235048 Hom.: 0 AF XY: 0.00000787 AC XY: 1 AN XY: 127062

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 SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000939

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.00e-7 AC: 1 AN: 1428880 Hom.: 0 Cov.: 31 AF XY: 0.00000142 AC XY: 1 AN XY: 705670

Gnomad4 AFR exome AF: 0.00

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: 9.17e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	0.0041	T
BayesDel_noAF	Uncertain	0.060
CADD	Benign	22
DANN	Uncertain	1.0
Eigen	Uncertain	0.65
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.25	T;T
M_CAP	Uncertain	0.11	D
MetaRNN	Uncertain	0.45	T;T
MetaSVM	Benign	-1.1	T
PROVEAN	Benign	-1.2	.;N
REVEL	Benign	0.20
Sift	Pathogenic	0.0	.;D
Vest4		0.55
MutPred		0.35		Gain of loop (P = 0.0045);Gain of loop (P = 0.0045);
MVP		0.53
ClinPred		0.99	D
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

Other links and lift over

dbSNP: rs776225870; hg19: chr9-136029575;