rs34638481

Positions:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_194318.4(B3GLCT):c.1105G>A(p.Gly369Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0263 in 1,613,940 control chromosomes in the GnomAD database, including 717 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.023 ( 69 hom., cov: 33)

Exomes 𝑓: 0.027 ( 648 hom. )

Consequence

B3GLCT
NM_194318.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.338

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 Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016687512).

BP6

Variant 13-31317606-G-A is Benign according to our data. Variant chr13-31317606-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 263091.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-31317606-G-A is described in Lovd as [Benign]. Variant chr13-31317606-G-A is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0232 (3534/152198) while in subpopulation NFE AF= 0.0335 (2281/68014). AF 95% confidence interval is 0.0324. There are 69 homozygotes in gnomad4. There are 1607 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 69 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
B3GLCT	NM_194318.4 link	c.1105G>A	p.Gly369Ser	missense_variant	13/15	ENST00000343307.5	NP_919299.3	Q6Y288

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
B3GLCT	ENST00000343307.5 link	c.1105G>A	p.Gly369Ser	missense_variant	13/15	1	NM_194318.4	ENSP00000343002.4		Q6Y288

Frequencies

GnomAD3 genomes

AF:

0.0232

AC:

3533

AN:

152080

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00707

Gnomad AMI

AF:

0.0285

Gnomad AMR

AF:

0.0247

Gnomad ASJ

AF:

0.0605

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0154

Gnomad FIN

AF:

0.0171

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.0335

Gnomad OTH

AF:

0.0335

GnomAD3 exomes

AF:

0.0252

AC:

6331

AN:

251446

Hom.:

125

AF XY:

0.0258

AC XY:

3512

AN XY:

135898

show subpopulations

Gnomad AFR exome

AF:

0.00627

Gnomad AMR exome

AF:

0.0199

Gnomad ASJ exome

AF:

0.0607

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0172

Gnomad FIN exome

AF:

0.0190

Gnomad NFE exome

AF:

0.0331

Gnomad OTH exome

AF:

0.0370

GnomAD4 exome

AF:

0.0266

AC:

38952

AN:

1461742

Hom.:

648

Cov.:

AF XY:

0.0268

AC XY:

19517

AN XY:

727176

show subpopulations

Gnomad4 AFR exome

AF:

0.00591

Gnomad4 AMR exome

AF:

0.0213

Gnomad4 ASJ exome

AF:

0.0587

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0174

Gnomad4 FIN exome

AF:

0.0216

Gnomad4 NFE exome

AF:

0.0284

Gnomad4 OTH exome

AF:

0.0297

GnomAD4 genome

AF:

0.0232

AC:

3534

AN:

152198

Hom.:

Cov.:

AF XY:

0.0216

AC XY:

1607

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.00705

Gnomad4 AMR

AF:

0.0247

Gnomad4 ASJ

AF:

0.0605

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0156

Gnomad4 FIN

AF:

0.0171

Gnomad4 NFE

AF:

0.0335

Gnomad4 OTH

AF:

0.0332

Alfa

AF:

0.0313

Hom.:

137

Bravo

AF:

0.0226

TwinsUK

AF:

0.0240

AC:

ALSPAC

AF:

0.0280

AC:

108

ESP6500AA

AF:

0.00704

AC:

ESP6500EA

AF:

0.0336

AC:

289

ExAC

AF:

0.0263

AC:

3192

Asia WGS

AF:

0.00808

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 05, 2018	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -

Peters plus syndrome

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	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. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.53

CADD

Benign

0.0060

DANN

Benign

0.85

DEOGEN2

Benign

0.026

Eigen

Benign

-1.9

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.60

MetaRNN

Benign

0.0017

MetaSVM

Benign

-0.86

MutationAssessor

Benign

-1.5

PrimateAI

Benign

0.24

PROVEAN

Benign

2.2

REVEL

Benign

0.15

Sift

Benign

1.0

Sift4G

Benign

0.91

Polyphen

0.0

Vest4

0.058

MPC

0.22

ClinPred

0.0019

GERP RS

-3.2

Varity_R

0.021

gMVP

0.25

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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