NM_021996.6:c.829A>G

Variant names:

• chr9-133153792-T-C
• rs1588581381
• NM_021996.6:c.829A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_021996.6(GBGT1):​c.829A>G​(p.Arg277Gly) 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. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GBGT1 NM_021996.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0730

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13000497).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GBGT1	NM_021996.6	c.829A>G	p.Arg277Gly	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.829A>G	p.Arg277Gly	missense_variant	Exon 7 of 7	1	NM_021996.6	ENSP00000361110.3
ENSG00000285245	ENST00000647146.1	c.396+1386A>G		intron_variant	Intron 6 of 22			ENSP00000493691.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 24, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.829A>G (p.R277G) alteration is located in exon 7 (coding exon 6) of the GBGT1 gene. This alteration results from a A to G substitution at nucleotide position 829, causing the arginine (R) at amino acid position 277 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.052	T;.
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.59
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.65	T;T
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.13	T;T
MetaSVM	Benign	-0.93	T
PROVEAN	Benign	-2.1	N;N
REVEL	Benign	0.030
Sift	Benign	0.062	T;T
Sift4G	Benign	0.21	T;T
Polyphen		0.0020	B;.
Vest4		0.14
MutPred		0.64		Loss of stability (P = 0.0551);.;
MVP		0.27
MPC		0.12
ClinPred		0.16	T
GERP RS		0.73
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.092
gMVP		0.49

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: rs1588581381; hg19: chr9-136029179;