NM_021996.6:c.58C>G

Variant names:

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

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>G​(p.Leu20Val) 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. 12/21 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: 27 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=0.109612554).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GBGT1	NM_021996.6	MANE Select	c.58C>G	p.Leu20Val	missense	Exon 2 of 7	NP_068836.2
	GBGT1	NM_001282632.2		c.58C>G	p.Leu20Val	missense	Exon 2 of 6	NP_001269561.1
	GBGT1	NM_001282629.2		c.58C>G	p.Leu20Val	missense	Exon 2 of 7	NP_001269558.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GBGT1	ENST00000372040.9	TSL:1 MANE Select	c.58C>G	p.Leu20Val	missense	Exon 2 of 7	ENSP00000361110.3
	ENSG00000285245	ENST00000647146.1		c.58C>G	p.Leu20Val	missense	Exon 2 of 23	ENSP00000493691.1
	GBGT1	ENST00000470431.5	TSL:1	c.58C>G	p.Leu20Val	missense	Exon 2 of 6	ENSP00000495017.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	15
DANN	Uncertain	1.0
DEOGEN2	Benign	0.035	T
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.81
FATHMM_MKL	Benign	0.063	N
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		-0.020
PROVEAN	Benign	-0.31	N
REVEL	Benign	0.041
Sift	Uncertain	0.0050	D
Sift4G	Benign	0.37	T
Polyphen		0.024	B
Vest4		0.045
MutPred		0.26		Loss of helix (P = 0.0376)
MVP		0.20
MPC		0.16
ClinPred		0.098	T
GERP RS		0.89
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.10
gMVP		0.51
Mutation Taster		=94/6	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;