Genetic Variant NM_021996.6:c.697G>A (chr9-133153924-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_021996.6(GBGT1):c.697G>A(p.Ala233Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000665 in 1,609,268 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000061 ( 0 hom. )

Consequence

GBGT1
NM_021996.6 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.65

Publications

1 publications found

Variant links:

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]

GBGT1 links:

ENSG00000285245 (HGNC:):

ENSG00000285245 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.02122888).

BP6

Variant 9-133153924-C-T is Benign according to our data. Variant chr9-133153924-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2371758.Status of the report is criteria_provided_single_submitter, 1 stars.

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GBGT1	NM_021996.6	MANE Select	c.697G>A	p.Ala233Thr	missense	Exon 7 of 7	NP_068836.2
GBGT1	NM_001282632.2		c.646G>A	p.Ala216Thr	missense	Exon 6 of 6	NP_001269561.1	Q8N5D6-3
GBGT1	NM_001288572.2		c.556G>A	p.Ala186Thr	missense	Exon 7 of 7	NP_001275501.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GBGT1	ENST00000372040.9	TSL:1 MANE Select	c.697G>A	p.Ala233Thr	missense	Exon 7 of 7	ENSP00000361110.3	Q8N5D6-1
GBGT1	ENST00000470431.5	TSL:1	c.*1250G>A		3_prime_UTR	Exon 6 of 6	ENSP00000495017.1	J7PW20
ENSG00000285245	ENST00000647146.1		c.396+1254G>A		intron	N/A	ENSP00000493691.1	A0A2R8Y471

Frequencies

GnomAD3 genomes

AF:

0.000118

AC:

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000999

AC:

AN:

250224

AF XY:

0.0000961

show subpopulations

Gnomad AFR exome

AF:

0.000554

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000927

Gnomad NFE exome

AF:

0.000124

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000611

AC:

AN:

1456920

Hom.:

Cov.:

AF XY:

0.0000525

AC XY:

AN XY:

723758

show subpopulations

African (AFR)

AF:

0.000269

AC:

AN:

33400

American (AMR)

AF:

0.00

AC:

AN:

44616

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26012

East Asian (EAS)

AF:

0.0000253

AC:

AN:

39532

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86140

European-Finnish (FIN)

AF:

0.0000941

AC:

AN:

53146

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5752

European-Non Finnish (NFE)

AF:

0.0000632

AC:

AN:

1108172

Other (OTH)

AF:

0.0000499

AC:

AN:

60150

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000118

AC:

AN:

152348

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74498

show subpopulations

African (AFR)

AF:

0.000337

AC:

AN:

41582

American (AMR)

AF:

0.00

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

68032

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000695

Hom.:

Bravo

AF:

0.000132

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000107

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000178

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.0020

(source)

DANN

Benign

0.88

DEOGEN2

Benign

0.022

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.036

LIST_S2

Benign

0.080

M_CAP

Benign

0.0078

MetaRNN

Benign

0.021

MetaSVM

Benign

-0.92

PhyloP100

-2.7

PROVEAN

Benign

-0.94

REVEL

Benign

0.014

Sift

Benign

0.35

Sift4G

Benign

0.60

Polyphen

0.0070

Vest4

0.031

MVP

0.10

MPC

0.091

ClinPred

0.023

GERP RS

-6.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.019

gMVP

0.31

Mutation Taster

=97/3

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over