rs202004832

Variant names:

• chr9-133153620-C-A
• rs202004832
• NM_021996.6:c.1001G>T

Your query was ambiguous. Multiple possible variants found:

• chr9-133153620-C-A
• chr9-133153620-C-G
• chr9-133153620-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_021996.6(GBGT1):​c.1001G>T​(p.Arg334Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000696 in 1,437,344 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R334H) has been classified as Uncertain significance.

• 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: 3.62
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.842

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021996.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GBGT1	NM_021996.6	MANE Select	c.1001G>T	p.Arg334Leu	missense	Exon 7 of 7	NP_068836.2
	GBGT1	NM_001282632.2		c.950G>T	p.Arg317Leu	missense	Exon 6 of 6	NP_001269561.1	Q8N5D6-3
	GBGT1	NM_001288572.2		c.860G>T	p.Arg287Leu	missense	Exon 7 of 7	NP_001275501.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GBGT1	ENST00000372040.9	TSL:1 MANE Select	c.1001G>T	p.Arg334Leu	missense	Exon 7 of 7	ENSP00000361110.3	Q8N5D6-1
	GBGT1	ENST00000470431.5	TSL:1	c.*1554G>T		3_prime_UTR	Exon 6 of 6	ENSP00000495017.1	J7PW20
	ENSG00000285245	ENST00000647146.1		c.396+1558G>T		intron	N/A	ENSP00000493691.1	A0A2R8Y471

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.96e-7 AC: 1 AN: 1437344 Hom.: 0 Cov.: 31 AF XY: 0.00000140 AC XY: 1 AN XY: 712780

African (AFR) AF: 0.00 AC: 0 AN: 32640

American (AMR) AF: 0.00 AC: 0 AN: 41488

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24526

East Asian (EAS) AF: 0.00 AC: 0 AN: 39410

South Asian (SAS) AF: 0.0000121 AC: 1 AN: 82454

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52518

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5636

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1099386

Other (OTH) AF: 0.00 AC: 0 AN: 59286

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.10
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	T
Eigen	Pathogenic	0.82
Eigen_PC	Pathogenic	0.75
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.056	D
MetaRNN	Pathogenic	0.84	D
MetaSVM	Benign	-1.2	T
MutationAssessor	Pathogenic	3.5	H
PhyloP100		3.6
PROVEAN	Pathogenic	-6.1	D
REVEL	Uncertain	0.45
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.84
MutPred		0.65		Loss of phosphorylation at T337 (P = 0.0459)
MVP		0.42
MPC		0.52
ClinPred		0.99	D
GERP RS		5.2
Varity_R		0.77
gMVP		0.74
Mutation Taster		=56/44	polymorphism

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

Other links and lift over

dbSNP: rs202004832; hg19: chr9-136029007;