rs34830061

chr13-31274581-G-Achr13-31274581-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_194318.4(B3GLCT):c.733G>A(p.Val245Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00679 in 1,614,160 control chromosomes in the GnomAD database, including 71 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 0.0050 (5 hom., cov: 33)
  • Exomes 𝑓: 0.0070 (66 hom.)
• Consequence: B3GLCT NM_194318.4 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.220

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0038720667).
• BP6: Variant 13-31274581-G-A is Benign according to our data. Variant chr13-31274581-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 96630.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-31274581-G-A is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00503 (766/152316) while in subpopulation SAS AF= 0.00973 (47/4828). AF 95% confidence interval is 0.00752. There are 5 homozygotes in gnomad4. There are 372 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
B3GLCT	NM_194318.4	c.733G>A	p.Val245Met	missense_variant	9/15	ENST00000343307.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
B3GLCT	ENST00000343307.5	c.733G>A	p.Val245Met	missense_variant	9/15	1	NM_194318.4	P1
B3GLCT	ENST00000461652.2	n.348G>A		non_coding_transcript_exon_variant	4/7	3

Frequencies

GnomAD3 genomes AF: 0.00504 AC: 767 AN: 152198 Hom.: 5 Cov.: 33

Gnomad AFR AF: 0.00130

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.00275

Gnomad ASJ AF: 0.0193

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00993

Gnomad FIN AF: 0.00283

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00722

Gnomad OTH AF: 0.00718

GnomAD3 exomes AF: 0.00638 AC: 1605 AN: 251456 Hom.: 15 AF XY: 0.00668 AC XY: 908 AN XY: 135900

Gnomad AFR exome AF: 0.00141

Gnomad AMR exome AF: 0.00301

Gnomad ASJ exome AF: 0.0143

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00941

Gnomad FIN exome AF: 0.00328

Gnomad NFE exome AF: 0.00828

Gnomad OTH exome AF: 0.00522

GnomAD4 exome AF: 0.00697 AC: 10188 AN: 1461844 Hom.: 66 Cov.: 33 AF XY: 0.00709 AC XY: 5153 AN XY: 727230

Gnomad4 AFR exome AF: 0.00116

Gnomad4 AMR exome AF: 0.00318

Gnomad4 ASJ exome AF: 0.0153

Gnomad4 EAS exome AF: 0.0000756

Gnomad4 SAS exome AF: 0.00919

Gnomad4 FIN exome AF: 0.00359

Gnomad4 NFE exome AF: 0.00733

Gnomad4 OTH exome AF: 0.00657

GnomAD4 genome AF: 0.00503 AC: 766 AN: 152316 Hom.: 5 Cov.: 33 AF XY: 0.00499 AC XY: 372 AN XY: 74478

Gnomad4 AFR AF: 0.00130

Gnomad4 AMR AF: 0.00275

Gnomad4 ASJ AF: 0.0193

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00973

Gnomad4 FIN AF: 0.00283

Gnomad4 NFE AF: 0.00722

Gnomad4 OTH AF: 0.00710

Alfa AF: 0.00694 Hom.: 3

Bravo AF: 0.00501

TwinsUK AF: 0.00755 AC: 28

ALSPAC AF: 0.00778 AC: 30

ESP6500AA AF: 0.00113 AC: 5

ESP6500EA AF: 0.00744 AC: 64

ExAC AF: 0.00696 AC: 845

Asia WGS AF: 0.00202 AC: 7 AN: 3478

EpiCase AF: 0.00682

EpiControl AF: 0.00776

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Dec 01, 2023	B3GLCT: BP4, BS2 -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	May 18, 2020	- -
Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Sep 25, 2017	- -

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia	Feb 16, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Apr 16, 2013	- -

Peters plus syndrome Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 19, 2024	- -
Likely 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.49
Cadd	Benign	6.5
Dann	Benign	0.91
DEOGEN2	Benign	0.037	T
Eigen	Benign	-0.79
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.049	N
LIST_S2	Benign	0.65	T
MetaRNN	Benign	0.0039	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.46	N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.14	N
REVEL	Benign	0.061
Sift	Benign	0.14	T
Sift4G	Benign	0.11	T
Polyphen		0.069	B
Vest4		0.18
MVP		0.50
MPC		0.22
ClinPred		0.00022	T
GERP RS		1.8
Varity_R		0.021
gMVP		0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs34830061; hg19: chr13-31848718;