Genetic Variant B3GLCT:p.Gln38Arg (chr13-31215093-A-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_194318.4(B3GLCT):c.113A>G(p.Gln38Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000292 in 1,611,270 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000032 ( 0 hom. )

Consequence

B3GLCT
NM_194318.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.303

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0387685).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
B3GLCT	NM_194318.4 link	c.113A>G	p.Gln38Arg	missense_variant	Exon 2 of 15	ENST00000343307.5	NP_919299.3	Q6Y288
B3GLCT	XM_006719768.4 link	c.56A>G	p.Gln19Arg	missense_variant	Exon 2 of 15		XP_006719831.1
B3GLCT	XM_011534936.2 link	c.113A>G	p.Gln38Arg	missense_variant	Exon 2 of 14		XP_011533238.1
B3GLCT	XM_047430111.1 link	c.113A>G	p.Gln38Arg	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.113A>G	p.Gln38Arg	missense_variant	Exon 2 of 15	1	NM_194318.4	ENSP00000343002.4		Q6Y288

Frequencies

GnomAD3 genomes

AF:

0.00000659

AC:

AN:

151796

Hom.:

Cov.:

show subpopulations

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000315

AC:

AN:

1459474

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

726032

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:

0.00

Gnomad4 NFE exome

AF:

0.0000387

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.00000659

AC:

AN:

151796

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74118

show subpopulations

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:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.0000151

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Dec 02, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.113A>G (p.Q38R) alteration is located in exon 2 (coding exon 2) of the B3GLCT gene. This alteration results from a A to G substitution at nucleotide position 113, causing the glutamine (Q) at amino acid position 38 to be replaced by an arginine (R). 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

0.062

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.60

CADD

Benign

2.2

DANN

Benign

0.64

DEOGEN2

Benign

0.048

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.018

LIST_S2

Benign

0.47

M_CAP

Benign

0.011

MetaRNN

Benign

0.039

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.37

REVEL

Benign

0.081

Sift

Benign

0.56

Sift4G

Benign

0.60

Polyphen

0.0

Vest4

0.11

MutPred

0.076

Loss of methylation at K34 (P = 0.1301);

MVP

0.34

MPC

0.24

ClinPred

0.032

GERP RS

-3.0

Varity_R

0.035

gMVP

0.25

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