chr9-133153924-C-G

Variant names:

• chr9-133153924-C-G
• rs199834711
• NM_021996.6:c.697G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_021996.6(GBGT1):​c.697G>C​(p.Ala233Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A233T) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GBGT1 NM_021996.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.65
• Publications: 1 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10345173).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GBGT1	NM_021996.6	MANE Select	c.697G>C	p.Ala233Pro	missense	Exon 7 of 7	NP_068836.2
	GBGT1	NM_001282632.2		c.646G>C	p.Ala216Pro	missense	Exon 6 of 6	NP_001269561.1	Q8N5D6-3
	GBGT1	NM_001288572.2		c.556G>C	p.Ala186Pro	missense	Exon 7 of 7	NP_001275501.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GBGT1	ENST00000372040.9	TSL:1 MANE Select	c.697G>C	p.Ala233Pro	missense	Exon 7 of 7	ENSP00000361110.3	Q8N5D6-1
	GBGT1	ENST00000470431.5	TSL:1	c.*1250G>C		3_prime_UTR	Exon 6 of 6	ENSP00000495017.1	J7PW20
	ENSG00000285245	ENST00000647146.1		c.396+1254G>C		intron	N/A	ENSP00000493691.1	A0A2R8Y471

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	0.0050
DANN	Uncertain	0.98
DEOGEN2	Benign	0.046	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.071	N
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-0.99	T
PhyloP100		-2.7
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.031
Sift	Benign	0.066	T
Sift4G	Benign	0.25	T
Polyphen		0.087	B
Vest4		0.12
MutPred		0.52		Gain of disorder (P = 0.0458)
MVP		0.14
MPC		0.30
ClinPred		0.082	T
GERP RS		-6.3
Varity_R		0.12
gMVP		0.61
Mutation Taster		=91/9	polymorphism

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: rs199834711; hg19: chr9-136029311;