NM_021996.6:c.363C>A

Variant names:

• chr9-133154258-G-T
• rs35898523
• NM_021996.6:c.363C>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_021996.6(GBGT1):​c.363C>A​(p.Tyr121*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0647 in 1,519,242 control chromosomes in the GnomAD database, including 3,502 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.060 (323 hom., cov: 32)
  • Exomes 𝑓: 0.065 (3179 hom.)
• Consequence: GBGT1 NM_021996.6 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.733
• Publications: 28 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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0705 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.363C>A	p.Tyr121*	stop_gained	Exon 7 of 7	NP_068836.2
	GBGT1	NM_001282632.2		c.312C>A	p.Tyr104*	stop_gained	Exon 6 of 6	NP_001269561.1
	GBGT1	NM_001288572.2		c.222C>A	p.Tyr74*	stop_gained	Exon 7 of 7	NP_001275501.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GBGT1	ENST00000372040.9	TSL:1 MANE Select	c.363C>A	p.Tyr121*	stop_gained	Exon 7 of 7	ENSP00000361110.3
	GBGT1	ENST00000470431.5	TSL:1	c.*916C>A		3_prime_UTR	Exon 6 of 6	ENSP00000495017.1
	ENSG00000285245	ENST00000647146.1		c.396+920C>A		intron	N/A	ENSP00000493691.1

Frequencies

GnomAD3 genomes AF: 0.0598 AC: 9100 AN: 152138 Hom.: 320 Cov.: 32

Gnomad AFR AF: 0.0409

Gnomad AMI AF: 0.0570

Gnomad AMR AF: 0.0432

Gnomad ASJ AF: 0.0813

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0548

Gnomad FIN AF: 0.101

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0722

Gnomad OTH AF: 0.0650

GnomAD2 exomes AF: 0.0578 AC: 10722 AN: 185574 AF XY: 0.0598

Gnomad AFR exome AF: 0.0412

Gnomad AMR exome AF: 0.0334

Gnomad ASJ exome AF: 0.0872

Gnomad EAS exome AF: 0.000180

Gnomad FIN exome AF: 0.105

Gnomad NFE exome AF: 0.0706

Gnomad OTH exome AF: 0.0621

GnomAD4 exome AF: 0.0653 AC: 89199 AN: 1366986 Hom.: 3179 Cov.: 28 AF XY: 0.0657 AC XY: 43960 AN XY: 669032

African (AFR) AF: 0.0432 AC: 1337 AN: 30944

American (AMR) AF: 0.0336 AC: 1153 AN: 34338

Ashkenazi Jewish (ASJ) AF: 0.0856 AC: 1776 AN: 20742

East Asian (EAS) AF: 0.000181 AC: 7 AN: 38688

South Asian (SAS) AF: 0.0551 AC: 4030 AN: 73172

European-Finnish (FIN) AF: 0.100 AC: 4766 AN: 47458

Middle Eastern (MID) AF: 0.109 AC: 579 AN: 5324

European-Non Finnish (NFE) AF: 0.0681 AC: 72152 AN: 1059982

Other (OTH) AF: 0.0603 AC: 3399 AN: 56338

GnomAD4 genome AF: 0.0598 AC: 9106 AN: 152256 Hom.: 323 Cov.: 32 AF XY: 0.0605 AC XY: 4501 AN XY: 74442

African (AFR) AF: 0.0409 AC: 1699 AN: 41566

American (AMR) AF: 0.0431 AC: 660 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0813 AC: 282 AN: 3470

East Asian (EAS) AF: 0.000580 AC: 3 AN: 5174

South Asian (SAS) AF: 0.0559 AC: 270 AN: 4830

European-Finnish (FIN) AF: 0.101 AC: 1068 AN: 10596

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0722 AC: 4910 AN: 68002

Other (OTH) AF: 0.0639 AC: 135 AN: 2114

Alfa AF: 0.0647 Hom.: 1058

Bravo AF: 0.0538

TwinsUK AF: 0.0628 AC: 233

ALSPAC AF: 0.0669 AC: 258

ESP6500AA AF: 0.0452 AC: 199

ESP6500EA AF: 0.0731 AC: 629

ExAC AF: 0.0572 AC: 6693

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.37
CADD	Pathogenic	34
DANN	Uncertain	0.99
Eigen	Uncertain	0.34
Eigen_PC	Benign	0.11
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.26	T
MetaRNN	Benign	0.0018	T
MetaSVM	Benign	-1.1	T
PhyloP100		0.73
PROVEAN	Benign	0.62	N
REVEL	Benign	0.015
Sift	Benign	0.60	T
Vest4		0.38
ClinPred		0.094	T
GERP RS		1.5
Mutation Taster		=178/22	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs35898523; hg19: chr9-136029645; COSMIC: COSV64410675; COSMIC: COSV64410675;