9-133162355-G-T

Variant names:

• chr9-133162355-G-T
• rs2073924
• NM_021996.6:c.58C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_021996.6(GBGT1):​c.58C>A​(p.Leu20Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict 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)
• Consequence: GBGT1 NM_021996.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0200
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1090582).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GBGT1	NM_021996.6	c.58C>A	p.Leu20Ile	missense_variant	Exon 2 of 7	ENST00000372040.9	NP_068836.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GBGT1	ENST00000372040.9	c.58C>A	p.Leu20Ile	missense_variant	Exon 2 of 7	1	NM_021996.6	ENSP00000361110.3
ENSG00000285245	ENST00000647146.1	c.58C>A	p.Leu20Ile	missense_variant	Exon 2 of 23			ENSP00000493691.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.035	.;T;.;.;.;.;.;.;.;.
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.054	N
LIST_S2	Benign	0.58	T;T;T;T;T;T;T;.;T;T
M_CAP	Benign	0.034	D
MetaRNN	Benign	0.11	T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.1	.;M;M;.;M;.;.;.;.;.
PhyloP100		-0.020
PROVEAN	Benign	-0.21	.;N;N;.;N;.;N;.;N;.
REVEL	Benign	0.052
Sift	Uncertain	0.0090	.;D;D;.;D;.;D;.;D;.
Sift4G	Benign	0.12	.;T;D;.;T;.;D;.;D;.
Polyphen		0.0010, 0.13	.;B;B;.;.;.;.;.;.;.
Vest4		0.078, 0.20, 0.13, 0.20, 0.13
MutPred		0.24		Gain of catalytic residue at L20 (P = 0.1064);Gain of catalytic residue at L20 (P = 0.1064);Gain of catalytic residue at L20 (P = 0.1064);Gain of catalytic residue at L20 (P = 0.1064);Gain of catalytic residue at L20 (P = 0.1064);Gain of catalytic residue at L20 (P = 0.1064);Gain of catalytic residue at L20 (P = 0.1064);Gain of catalytic residue at L20 (P = 0.1064);Gain of catalytic residue at L20 (P = 0.1064);Gain of catalytic residue at L20 (P = 0.1064);
MVP		0.20
MPC		0.11
ClinPred		0.084	T
GERP RS		0.89
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.11
gMVP		0.36
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs2073924; hg19: chr9-136037742;