9-133154257-T-C

Variant summary

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

The NM_021996.6(GBGT1):c.364A>G(p.Thr122Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000438 in 1,369,308 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/17 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)
  • Exomes 𝑓: 0.0000044 (0 hom.)
• Consequence: GBGT1 NM_021996.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.420

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]

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=0.16368482).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GBGT1	NM_021996.6	c.364A>G	p.Thr122Ala	missense_variant	7/7	ENST00000372040.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GBGT1	ENST00000372040.9	c.364A>G	p.Thr122Ala	missense_variant	7/7	1	NM_021996.6	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000108 AC: 2 AN: 185848 Hom.: 0 AF XY: 0.0000101 AC XY: 1 AN XY: 98610

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000602

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000116

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000438 AC: 6 AN: 1369308 Hom.: 0 Cov.: 28 AF XY: 0.00000597 AC XY: 4 AN XY: 670088

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000517

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000377

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 03, 2023

The c.364A>G (p.T122A) 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 364, causing the threonine (T) at amino acid position 122 to be replaced by an alanine (A). 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	0.079
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.44
Cadd	Benign	19
Dann	Uncertain	0.99
Eigen	Benign	0.095
Eigen_PC	Benign	0.084
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.26	T;T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.16	T;T
MetaSVM	Benign	-0.66	T
MutationTaster	Benign	1.0	D;D;D;N;D
Vest4		0.50
MutPred		0.20		Gain of MoRF binding (P = 0.057);Gain of MoRF binding (P = 0.057);
MVP		0.40
ClinPred		0.20	T
GERP RS		5.4

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: rs962912980; hg19: chr9-136029644;