Genetic Variant B3GLCT:p.Cys6Phe (chr13-31200101-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_194318.4(B3GLCT):c.17G>T(p.Cys6Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000816 in 1,225,398 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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. C6Y) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 8.2e-7 ( 0 hom. )

Consequence

B3GLCT
NM_194318.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.742

Publications

0 publications found

Variant links:

Genes affected

B3GLCT (HGNC:20207): (beta 3-glucosyltransferase) The protein encoded by this gene is a beta-1,3-glucosyltransferase that transfers glucose to O-linked fucosylglycans on thrombospondin type-1 repeats (TSRs) of several proteins. The encoded protein is a type II membrane protein. Defects in this gene are a cause of Peters-plus syndrome (PPS).[provided by RefSeq, Mar 2009]

B3GLCT Gene-Disease associations (from GenCC):

Peters plus syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: PanelApp Australia, Orphanet, G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)

B3GLCT links:

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ACMG classification

Classification was made for transcript

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=0.0822458).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_194318.4. 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
	B3GLCT	NM_194318.4	MANE Select	c.17G>T	p.Cys6Phe	missense	Exon 1 of 15	NP_919299.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
B3GLCT	ENST00000343307.5	TSL:1 MANE Select	c.17G>T	p.Cys6Phe	missense	Exon 1 of 15	ENSP00000343002.4	Q6Y288
B3GLCT	ENST00000873566.1		c.17G>T	p.Cys6Phe	missense	Exon 1 of 13	ENSP00000543625.1
B3GLCT	ENST00000946543.1		c.17G>T	p.Cys6Phe	missense	Exon 1 of 11	ENSP00000616602.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

8.16e-7

AC:

AN:

1225398

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

603722

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24648

American (AMR)

AF:

0.00

AC:

AN:

23624

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19860

East Asian (EAS)

AF:

0.00

AC:

AN:

23310

South Asian (SAS)

AF:

0.00

AC:

AN:

66348

European-Finnish (FIN)

AF:

0.00

AC:

AN:

28454

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3416

European-Non Finnish (NFE)

AF:

0.00000101

AC:

AN:

987702

Other (OTH)

AF:

0.00

AC:

AN:

48036

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.0049

BayesDel_noAF

Benign

-0.24

CADD

Benign

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.048

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.78

FATHMM_MKL

Benign

0.028

LIST_S2

Benign

0.39

M_CAP

Benign

0.017

MetaRNN

Benign

0.082

MetaSVM

Benign

-0.89

MutationAssessor

Benign

0.0

PhyloP100

0.74

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-0.40

REVEL

Benign

0.15

Sift

Pathogenic

0.0

Polyphen

0.0

Vest4

0.17

MutPred

0.55

Loss of catalytic residue at W7 (P = 0.0081)

MVP

0.49

MPC

0.33

ClinPred

0.38

GERP RS

2.2

PromoterAI

-0.0062

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.54

gMVP

0.25

Mutation Taster

=86/14

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over