rs147485868

chr13-31323773-G-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_Strong BP6

The NM_194318.4(B3GLCT):c.1207G>A(p.Val403Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00167 in 1,614,130 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.0012 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0017 (4 hom.)
• Consequence: B3GLCT NM_194318.4 missense
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:3 B:2
• Conservation: PhyloP100: 2.13

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 Likely_benign. Variant got -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.017538518).
• BP6: Variant 13-31323773-G-A is Benign according to our data. Variant chr13-31323773-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 425025.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=3}.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
B3GLCT	NM_194318.4	c.1207G>A	p.Val403Ile	missense_variant	14/15	ENST00000343307.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
B3GLCT	ENST00000343307.5	c.1207G>A	p.Val403Ile	missense_variant	14/15	1	NM_194318.4	P1

Frequencies

GnomAD3 genomes AF: 0.00121 AC: 184 AN: 152156 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000386

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000589

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.000755

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00213

Gnomad OTH AF: 0.000958

GnomAD3 exomes AF: 0.00119 AC: 298 AN: 251458 Hom.: 1 AF XY: 0.00125 AC XY: 170 AN XY: 135898

Gnomad AFR exome AF: 0.000369

Gnomad AMR exome AF: 0.000376

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.000326

Gnomad SAS exome AF: 0.000327

Gnomad FIN exome AF: 0.00120

Gnomad NFE exome AF: 0.00202

Gnomad OTH exome AF: 0.000978

GnomAD4 exome AF: 0.00172 AC: 2509 AN: 1461856 Hom.: 4 Cov.: 31 AF XY: 0.00163 AC XY: 1184 AN XY: 727234

Gnomad4 AFR exome AF: 0.000329

Gnomad4 AMR exome AF: 0.000335

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.000101

Gnomad4 SAS exome AF: 0.000255

Gnomad4 FIN exome AF: 0.00114

Gnomad4 NFE exome AF: 0.00209

Gnomad4 OTH exome AF: 0.00114

GnomAD4 genome AF: 0.00121 AC: 184 AN: 152274 Hom.: 0 Cov.: 32 AF XY: 0.00110 AC XY: 82 AN XY: 74464

Gnomad4 AFR AF: 0.000385

Gnomad4 AMR AF: 0.000588

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000621

Gnomad4 FIN AF: 0.000755

Gnomad4 NFE AF: 0.00213

Gnomad4 OTH AF: 0.000948

Alfa AF: 0.00172 Hom.: 1

Bravo AF: 0.00107

TwinsUK AF: 0.00162 AC: 6

ALSPAC AF: 0.00234 AC: 9

ESP6500AA AF: 0.000681 AC: 3

ESP6500EA AF: 0.00128 AC: 11

ExAC AF: 0.00116 AC: 141

EpiCase AF: 0.00158

EpiControl AF: 0.00119

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:3 Benign:2

Revision: criteria provided, conflicting classifications

Submissions by phenotype

Peters plus syndrome Uncertain:2 Benign:1

Uncertain significance, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -
Likely benign, criteria provided, single submitter	clinical testing	Invitae	Dec 25, 2023	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Jul 01, 2016	- -

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Oct 01, 2016

- -

B3GLCT-related condition Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 27, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.28
Cadd	Benign	12
Dann	Benign	0.73
DEOGEN2	Benign	0.057	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.48	N
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.018	T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	1.9	L
MutationTaster	Benign	0.77	D
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.32	N
REVEL	Uncertain	0.30
Sift	Benign	0.52	T
Sift4G	Benign	0.39	T
Polyphen		0.048	B
Vest4		0.24
MVP		0.33
MPC		0.20
ClinPred		0.015	T
GERP RS		-9.3
Varity_R		0.018
gMVP		0.30

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: rs147485868; hg19: chr13-31897910; COSMIC: COSV58453697;