rs547647945

Variant names:

• chr9-133154155-C-T
• rs547647945
• NM_021996.6:c.466G>A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_021996.6(GBGT1):​c.466G>A​(p.Gly156Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000332 in 1,596,734 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000033 (0 hom.)
• Consequence: GBGT1 NM_021996.6 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.631

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 Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.036347687).
• BP6: Variant 9-133154155-C-T is Benign according to our data. Variant chr9-133154155-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2349705.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GBGT1	NM_021996.6	c.466G>A	p.Gly156Arg	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.466G>A	p.Gly156Arg	missense_variant	Exon 7 of 7	1	NM_021996.6	ENSP00000361110.3
ENSG00000285245	ENST00000647146.1	c.396+1023G>A		intron_variant	Intron 6 of 22			ENSP00000493691.1

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152188 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000647 AC: 16 AN: 247410 Hom.: 0 AF XY: 0.0000298 AC XY: 4 AN XY: 134076

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000206

Gnomad ASJ exome AF: 0.000103

Gnomad EAS exome AF: 0.0000547

Gnomad SAS exome AF: 0.0000330

Gnomad FIN exome AF: 0.000140

Gnomad NFE exome AF: 0.00000898

Gnomad OTH exome AF: 0.000331

GnomAD4 exome AF: 0.0000332 AC: 48 AN: 1444428 Hom.: 0 Cov.: 32 AF XY: 0.0000238 AC XY: 17 AN XY: 714848

Gnomad4 AFR exome AF: 0.0000905

Gnomad4 AMR exome AF: 0.000294

Gnomad4 ASJ exome AF: 0.0000388

Gnomad4 EAS exome AF: 0.000102

Gnomad4 SAS exome AF: 0.0000233

Gnomad4 FIN exome AF: 0.0000956

Gnomad4 NFE exome AF: 0.0000155

Gnomad4 OTH exome AF: 0.0000336

GnomAD4 genome AF: 0.0000328 AC: 5 AN: 152306 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74472

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.000261

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000756

ExAC AF: 0.0000577 AC: 7

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Jul 29, 2022

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.28
DANN	Benign	0.51
DEOGEN2	Benign	0.010	T;.
Eigen	Benign	-1.9
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.055	N
LIST_S2	Benign	0.36	T;T
M_CAP	Benign	0.0062	T
MetaRNN	Benign	0.036	T;T
MetaSVM	Benign	-0.91	T
PROVEAN	Benign	1.5	N;N
REVEL	Benign	0.0030
Sift	Benign	1.0	T;T
Sift4G	Benign	0.67	T;T
Polyphen		0.0	B;.
Vest4		0.039
MutPred		0.32		Loss of catalytic residue at V157 (P = 0.0154);.;
MVP		0.21
MPC		0.10
ClinPred		0.0071	T
GERP RS		-1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.026
gMVP		0.38

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs547647945; hg19: chr9-136029542;