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

Variant summary

Our verdict is Likely benign. Variant got -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. 16/21 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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
B3GLCT	NM_194318.4 link	c.95C>A	p.Thr32Lys	missense_variant	Exon 2 of 15	ENST00000343307.5	NP_919299.3	Q6Y288
B3GLCT	XM_006719768.4 link	c.38C>A	p.Thr13Lys	missense_variant	Exon 2 of 15		XP_006719831.1
B3GLCT	XM_011534936.2 link	c.95C>A	p.Thr32Lys	missense_variant	Exon 2 of 14		XP_011533238.1
B3GLCT	XM_047430111.1 link	c.95C>A	p.Thr32Lys	missense_variant	Exon 2 of 12		XP_047286067.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
B3GLCT	ENST00000343307.5 link	c.95C>A	p.Thr32Lys	missense_variant	Exon 2 of 15	1	NM_194318.4	ENSP00000343002.4		Q6Y288

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

149482

Hom.:

Cov.:

FAILED QC

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

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000393

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

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

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000598

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Jun 29, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.95C>A (p.T32K) alteration is located in exon 2 (coding exon 2) of the B3GLCT gene. This alteration results from a C to A substitution at nucleotide position 95, causing the threonine (T) at amino acid position 32 to be replaced by a lysine (K). 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

0.068

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

0.47

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

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

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over