9-133154258-G-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 0P and 3B. BP4_Moderate BP7

The NM_021996.6(GBGT1):​c.363C>T​(p.Tyr121Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000139 in 1,368,076 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: GBGT1 NM_021996.6 synonymous
• 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: Likely_benign. The variant received -3 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.106027484).
• BP7: Synonymous conserved (PhyloP=0.733 with no splicing effect.

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>T	p.Tyr121Tyr	synonymous	Exon 7 of 7	NP_068836.2
	GBGT1	NM_001282632.2		c.312C>T	p.Tyr104Tyr	synonymous	Exon 6 of 6	NP_001269561.1
	GBGT1	NM_001288572.2		c.222C>T	p.Tyr74Tyr	synonymous	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>T	p.Tyr121Tyr	synonymous	Exon 7 of 7	ENSP00000361110.3
	GBGT1	ENST00000470431.5	TSL:1	c.*916C>T		3_prime_UTR	Exon 6 of 6	ENSP00000495017.1
	ENSG00000285245	ENST00000647146.1		c.396+920C>T		intron	N/A	ENSP00000493691.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000431 AC: 8 AN: 185574 AF XY: 0.0000102

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000228

GnomAD4 exome AF: 0.0000139 AC: 19 AN: 1368076 Hom.: 0 Cov.: 28 AF XY: 0.0000105 AC XY: 7 AN XY: 669520

African (AFR) AF: 0.00 AC: 0 AN: 30962

American (AMR) AF: 0.00 AC: 0 AN: 34344

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20746

East Asian (EAS) AF: 0.00 AC: 0 AN: 38690

South Asian (SAS) AF: 0.000232 AC: 17 AN: 73200

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47502

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5326

European-Non Finnish (NFE) AF: 9.43e-7 AC: 1 AN: 1060922

Other (OTH) AF: 0.0000177 AC: 1 AN: 56384

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 1058

Bravo AF: 0.00000378

ExAC AF: 0.00000854 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	1.8
DANN	Benign	0.75
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.22
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.31	T
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.1	T
PhyloP100		0.73
PROVEAN	Benign	0.24	N
REVEL	Benign	0.0070
Sift	Benign	0.090	T
Vest4		0.41
MutPred		0.30		Gain of sheet (P = 0.0149)
MVP		0.21
ClinPred		0.039	T
GERP RS		1.5
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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;