Genetic Variant B3GLCT:p.Thr32Lys (chr13-31215075-C-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_194318.4(B3GLCT):c.95C>A(p.Thr32Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

B3GLCT
NM_194318.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.367

Publications

1 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.050738573).

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.95C>A	p.Thr32Lys	missense	Exon 2 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.95C>A	p.Thr32Lys	missense	Exon 2 of 15	ENSP00000343002.4	Q6Y288
B3GLCT	ENST00000873566.1		c.95C>A	p.Thr32Lys	missense	Exon 2 of 13	ENSP00000543625.1
B3GLCT	ENST00000946543.1		c.95C>A	p.Thr32Lys	missense	Exon 2 of 11	ENSP00000616602.1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

149482

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000137

AC:

AN:

1456806

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

724778

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

33392

American (AMR)

AF:

0.00

AC:

AN:

44572

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26072

East Asian (EAS)

AF:

0.00

AC:

AN:

39606

South Asian (SAS)

AF:

0.00

AC:

AN:

85756

European-Finnish (FIN)

AF:

0.0000393

AC:

AN:

50950

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5742

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110450

Other (OTH)

AF:

0.00

AC:

AN:

60266

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.250

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

149482

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

72634

African (AFR)

AF:

0.00

AC:

AN:

40490

American (AMR)

AF:

0.00

AC:

AN:

14928

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3462

East Asian (EAS)

AF:

0.00

AC:

AN:

5116

South Asian (SAS)

AF:

0.00

AC:

AN:

4758

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9772

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67682

Other (OTH)

AF:

0.00

AC:

AN:

2054

Alfa

AF:

0.0000319

Hom.:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

0.47

(source)

DANN

Benign

0.52

DEOGEN2

Benign

0.047

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.020

LIST_S2

Benign

0.40

M_CAP

Benign

0.025

MetaRNN

Benign

0.051

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.69

PhyloP100

-0.37

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.75

REVEL

Benign

0.11

Sift

Benign

0.47

Sift4G

Benign

0.50

Polyphen

0.089

Vest4

0.22

MutPred

0.24

Gain of ubiquitination at T32 (P = 0.0121)

MVP

0.18

MPC

0.26

ClinPred

0.079

GERP RS

-6.3

Varity_R

0.062

gMVP

0.36

Mutation Taster

=96/4

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over