9-133154170-G-A

Variant names:

• chr9-133154170-G-A
• rs1452956294
• NM_021996.6:c.451C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_021996.6(GBGT1):​c.451C>T​(p.Pro151Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000139 in 1,440,602 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. P151A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: GBGT1 NM_021996.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.30
• 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 2 ACMG points.

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

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.451C>T	p.Pro151Ser	missense	Exon 7 of 7	NP_068836.2
	GBGT1	NM_001282632.2		c.400C>T	p.Pro134Ser	missense	Exon 6 of 6	NP_001269561.1	Q8N5D6-3
	GBGT1	NM_001288572.2		c.310C>T	p.Pro104Ser	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.451C>T	p.Pro151Ser	missense	Exon 7 of 7	ENSP00000361110.3	Q8N5D6-1
	GBGT1	ENST00000470431.5	TSL:1	c.*1004C>T		3_prime_UTR	Exon 6 of 6	ENSP00000495017.1	J7PW20
	ENSG00000285245	ENST00000647146.1		c.396+1008C>T		intron	N/A	ENSP00000493691.1	A0A2R8Y471

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000411 AC: 1 AN: 243080 AF XY: 0.00000759

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000548

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000139 AC: 2 AN: 1440602 Hom.: 0 Cov.: 32 AF XY: 0.00000281 AC XY: 2 AN XY: 712876

African (AFR) AF: 0.00 AC: 0 AN: 33040

American (AMR) AF: 0.00 AC: 0 AN: 43698

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25384

East Asian (EAS) AF: 0.0000510 AC: 2 AN: 39206

South Asian (SAS) AF: 0.00 AC: 0 AN: 85194

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52156

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5668

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1096844

Other (OTH) AF: 0.00 AC: 0 AN: 59412

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.095	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.018	T
MetaRNN	Uncertain	0.55	D
MetaSVM	Benign	-1.1	T
PhyloP100		6.3
PROVEAN	Pathogenic	-6.0	D
REVEL	Benign	0.28
Sift	Benign	0.036	D
Sift4G	Uncertain	0.030	D
Polyphen		1.0	D
Vest4		0.48
MutPred		0.53		Loss of glycosylation at T148 (P = 0.2926)
MVP		0.37
MPC		0.47
ClinPred		0.85	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.21
gMVP		0.72
Mutation Taster		=75/25	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1452956294; hg19: chr9-136029557;