9-133162355-G-A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021996.6(GBGT1):​c.58C>T​(p.Leu20Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 1,248,388 control chromosomes in the GnomAD database, including 21,095 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 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: 𝑓 0.23 (4709 hom., cov: 32)
  • Exomes 𝑓: 0.11 (16386 hom.)
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.3922324E-4).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.531 is higher than 0.05.

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>T	p.Leu20Phe	missense	Exon 2 of 7	NP_068836.2
	GBGT1	NM_001282632.2		c.58C>T	p.Leu20Phe	missense	Exon 2 of 6	NP_001269561.1
	GBGT1	NM_001282629.2		c.58C>T	p.Leu20Phe	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>T	p.Leu20Phe	missense	Exon 2 of 7	ENSP00000361110.3
	ENSG00000285245	ENST00000647146.1		c.58C>T	p.Leu20Phe	missense	Exon 2 of 23	ENSP00000493691.1
	GBGT1	ENST00000470431.5	TSL:1	c.58C>T	p.Leu20Phe	missense	Exon 2 of 6	ENSP00000495017.1

Frequencies

GnomAD3 genomes AF: 0.229 AC: 33891 AN: 148106 Hom.: 4702 Cov.: 32

Gnomad AFR AF: 0.255

Gnomad AMI AF: 0.297

Gnomad AMR AF: 0.239

Gnomad ASJ AF: 0.156

Gnomad EAS AF: 0.551

Gnomad SAS AF: 0.324

Gnomad FIN AF: 0.201

Gnomad MID AF: 0.194

Gnomad NFE AF: 0.188

Gnomad OTH AF: 0.227

GnomAD2 exomes AF: 0.114 AC: 19511 AN: 171460 AF XY: 0.106

Gnomad AFR exome AF: 0.142

Gnomad AMR exome AF: 0.115

Gnomad ASJ exome AF: 0.0411

Gnomad EAS exome AF: 0.455

Gnomad FIN exome AF: 0.125

Gnomad NFE exome AF: 0.0681

Gnomad OTH exome AF: 0.121

GnomAD4 exome AF: 0.106 AC: 116128 AN: 1100172 Hom.: 16386 Cov.: 31 AF XY: 0.114 AC XY: 62925 AN XY: 552954

African (AFR) AF: 0.140 AC: 3404 AN: 24306

American (AMR) AF: 0.145 AC: 4802 AN: 33132

Ashkenazi Jewish (ASJ) AF: 0.101 AC: 2259 AN: 22330

East Asian (EAS) AF: 0.524 AC: 17541 AN: 33468

South Asian (SAS) AF: 0.235 AC: 15286 AN: 65058

European-Finnish (FIN) AF: 0.191 AC: 9447 AN: 49370

Middle Eastern (MID) AF: 0.144 AC: 712 AN: 4942

European-Non Finnish (NFE) AF: 0.0686 AC: 56324 AN: 820918

Other (OTH) AF: 0.136 AC: 6353 AN: 46648

GnomAD4 genome AF: 0.229 AC: 33932 AN: 148216 Hom.: 4709 Cov.: 32 AF XY: 0.235 AC XY: 16969 AN XY: 72236

African (AFR) AF: 0.256 AC: 10244 AN: 40094

American (AMR) AF: 0.239 AC: 3553 AN: 14848

Ashkenazi Jewish (ASJ) AF: 0.156 AC: 535 AN: 3432

East Asian (EAS) AF: 0.549 AC: 2705 AN: 4930

South Asian (SAS) AF: 0.326 AC: 1492 AN: 4578

European-Finnish (FIN) AF: 0.201 AC: 2072 AN: 10310

Middle Eastern (MID) AF: 0.198 AC: 57 AN: 288

European-Non Finnish (NFE) AF: 0.188 AC: 12538 AN: 66784

Other (OTH) AF: 0.229 AC: 470 AN: 2056

Alfa AF: 0.210 Hom.: 11404

Bravo AF: 0.240

TwinsUK AF: 0.190 AC: 706

ALSPAC AF: 0.193 AC: 742

ESP6500AA AF: 0.276 AC: 1215

ESP6500EA AF: 0.192 AC: 1652

ExAC AF: 0.244 AC: 29576

Asia WGS AF: 0.311 AC: 909 AN: 2934

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	16
DANN	Uncertain	1.0
DEOGEN2	Benign	0.037	T
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.045	N
LIST_S2	Benign	0.57	T
MetaRNN	Benign	0.00024	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.4	L
PhyloP100		-0.020
PROVEAN	Benign	-0.21	N
REVEL	Benign	0.036
Sift	Uncertain	0.025	D
Sift4G	Uncertain	0.028	D
Polyphen		0.0020	B
Vest4		0.036
MPC		0.11
ClinPred		0.0046	T
GERP RS		0.89
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.069
gMVP		0.48
Mutation Taster		=96/4	polymorphism (auto)

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; COSMIC: COSV64404474; COSMIC: COSV64404474;