NM_194318.4:c.1108G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_194318.4(B3GLCT):c.1108G>A(p.Glu370Lys) variant causes a missense change. The variant allele was found at a frequency of 0.748 in 1,613,678 control chromosomes in the GnomAD database, including 456,734 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.67 ( 36183 hom., cov: 31)

Exomes 𝑓: 0.76 ( 420551 hom. )

Consequence

B3GLCT
NM_194318.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 6.17

Publications

53 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: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Orphanet, G2P, PanelApp Australia

B3GLCT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.169308E-6).

BP6

Variant 13-31317609-G-A is Benign according to our data. Variant chr13-31317609-G-A is described in ClinVar as Benign. ClinVar VariationId is 96624.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.768 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
B3GLCT	NM_194318.4 link	c.1108G>A	p.Glu370Lys	missense_variant	Exon 13 of 15	ENST00000343307.5	NP_919299.3	Q6Y288

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
B3GLCT	ENST00000343307.5 link	c.1108G>A	p.Glu370Lys	missense_variant	Exon 13 of 15	1	NM_194318.4	ENSP00000343002.4		Q6Y288

Frequencies

GnomAD3 genomes

AF:

0.671

AC:

101919

AN:

151882

Hom.:

36180

Cov.:

show subpopulations

Gnomad AFR

AF:

0.418

Gnomad AMI

AF:

0.873

Gnomad AMR

AF:

0.752

Gnomad ASJ

AF:

0.830

Gnomad EAS

AF:

0.779

Gnomad SAS

AF:

0.768

Gnomad FIN

AF:

0.710

Gnomad MID

AF:

0.794

Gnomad NFE

AF:

0.773

Gnomad OTH

AF:

0.707

GnomAD2 exomes

AF:

0.749

AC:

188293

AN:

251428

AF XY:

0.756

show subpopulations

Gnomad AFR exome

AF:

0.405

Gnomad AMR exome

AF:

0.792

Gnomad ASJ exome

AF:

0.837

Gnomad EAS exome

AF:

0.786

Gnomad FIN exome

AF:

0.714

Gnomad NFE exome

AF:

0.774

Gnomad OTH exome

AF:

0.761

GnomAD4 exome

AF:

0.756

AC:

1105023

AN:

1461678

Hom.:

420551

Cov.:

AF XY:

0.758

AC XY:

551507

AN XY:

727158

show subpopulations

African (AFR)

AF:

0.401

AC:

13439

AN:

33474

American (AMR)

AF:

0.787

AC:

35205

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.838

AC:

21894

AN:

26132

East Asian (EAS)

AF:

0.758

AC:

30081

AN:

39694

South Asian (SAS)

AF:

0.762

AC:

65684

AN:

86254

European-Finnish (FIN)

AF:

0.710

AC:

37937

AN:

53398

Middle Eastern (MID)

AF:

0.742

AC:

4281

AN:

5768

European-Non Finnish (NFE)

AF:

0.766

AC:

851542

AN:

1111852

Other (OTH)

AF:

0.745

AC:

44960

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

14719

29438

44157

58876

73595

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20374

40748

61122

81496

101870

<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:

0.671

AC:

101952

AN:

152000

Hom.:

36183

Cov.:

AF XY:

0.673

AC XY:

49994

AN XY:

74294

show subpopulations

African (AFR)

AF:

0.417

AC:

17285

AN:

41426

American (AMR)

AF:

0.752

AC:

11504

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.830

AC:

2883

AN:

3472

East Asian (EAS)

AF:

0.779

AC:

4010

AN:

5148

South Asian (SAS)

AF:

0.767

AC:

3685

AN:

4802

European-Finnish (FIN)

AF:

0.710

AC:

7499

AN:

10560

Middle Eastern (MID)

AF:

0.796

AC:

234

AN:

294

European-Non Finnish (NFE)

AF:

0.773

AC:

52567

AN:

67994

Other (OTH)

AF:

0.708

AC:

1489

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.526

Heterozygous variant carriers

1497

2994

4491

5988

7485

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

798

1596

2394

3192

3990

<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:

0.736

Hom.:

113497

Bravo

AF:

0.663

TwinsUK

AF:

0.767

AC:

2843

ALSPAC

AF:

0.773

AC:

2978

ESP6500AA

AF:

0.416

AC:

1833

ESP6500EA

AF:

0.778

AC:

6691

ExAC

AF:

0.742

AC:

90132

Asia WGS

AF:

0.782

AC:

2718

AN:

3478

EpiCase

AF:

0.774

EpiControl

AF:

0.781

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Dec 10, 2014

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Peters plus syndrome

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:2

Jun 14, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.25

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.052

Eigen

Benign

-0.035

Eigen_PC

Benign

-0.080

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.96

MetaRNN

Benign

0.0000022

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.9

PhyloP100

6.2

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-1.8

REVEL

Benign

0.29

Sift

Benign

0.13

Sift4G

Benign

0.29

Polyphen

0.96

Vest4

0.26

MPC

0.34

ClinPred

0.034

GERP RS

3.2

Varity_R

0.098

gMVP

0.82

Mutation Taster

=91/9

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over