13-31247855-T-C

Variant names:

• chr13-31247855-T-C
• rs4943266
• NM_194318.4:c.348T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_194318.4(B3GLCT):​c.348T>C​(p.His116His) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.98 in 1,541,690 control chromosomes in the GnomAD database, including 740,651 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.97 (71544 hom., cov: 32)
  • Exomes 𝑓: 0.98 (669107 hom.)
• Consequence: B3GLCT NM_194318.4 splice_region, synonymous
• Scores: Splicing: ADA: 0.0005678
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: -0.312
• Publications: 21 publications found

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

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 13-31247855-T-C is Benign according to our data. Variant chr13-31247855-T-C is described in ClinVar as Benign. ClinVar VariationId is 96628.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.312 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
B3GLCT	NM_194318.4	c.348T>C	p.His116His	splice_region_variant, synonymous_variant	Exon 6 of 15	ENST00000343307.5	NP_919299.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
B3GLCT	ENST00000343307.5	c.348T>C	p.His116His	splice_region_variant, synonymous_variant	Exon 6 of 15	1	NM_194318.4	ENSP00000343002.4

Frequencies

GnomAD3 genomes AF: 0.969 AC: 147477 AN: 152180 Hom.: 71508 Cov.: 32

Gnomad AFR AF: 0.929

Gnomad AMI AF: 0.987

Gnomad AMR AF: 0.983

Gnomad ASJ AF: 0.993

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.994

Gnomad FIN AF: 0.993

Gnomad MID AF: 0.978

Gnomad NFE AF: 0.981

Gnomad OTH AF: 0.974

GnomAD2 exomes AF: 0.984 AC: 245398 AN: 249382 AF XY: 0.985

Gnomad AFR exome AF: 0.927

Gnomad AMR exome AF: 0.990

Gnomad ASJ exome AF: 0.996

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 0.993

Gnomad NFE exome AF: 0.982

Gnomad OTH exome AF: 0.987

GnomAD4 exome AF: 0.981 AC: 1363453 AN: 1389392 Hom.: 669107 Cov.: 21 AF XY: 0.982 AC XY: 683161 AN XY: 695672

African (AFR) AF: 0.926 AC: 29625 AN: 31994

American (AMR) AF: 0.989 AC: 44055 AN: 44540

Ashkenazi Jewish (ASJ) AF: 0.995 AC: 25417 AN: 25550

East Asian (EAS) AF: 1.00 AC: 39209 AN: 39210

South Asian (SAS) AF: 0.994 AC: 84075 AN: 84586

European-Finnish (FIN) AF: 0.992 AC: 52794 AN: 53210

Middle Eastern (MID) AF: 0.987 AC: 5422 AN: 5492

European-Non Finnish (NFE) AF: 0.980 AC: 1026107 AN: 1046938

Other (OTH) AF: 0.981 AC: 56749 AN: 57872

GnomAD4 genome AF: 0.969 AC: 147571 AN: 152298 Hom.: 71544 Cov.: 32 AF XY: 0.971 AC XY: 72283 AN XY: 74474

African (AFR) AF: 0.928 AC: 38568 AN: 41548

American (AMR) AF: 0.983 AC: 15038 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.993 AC: 3446 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5174 AN: 5174

South Asian (SAS) AF: 0.994 AC: 4795 AN: 4822

European-Finnish (FIN) AF: 0.993 AC: 10545 AN: 10616

Middle Eastern (MID) AF: 0.976 AC: 287 AN: 294

European-Non Finnish (NFE) AF: 0.981 AC: 66757 AN: 68040

Other (OTH) AF: 0.974 AC: 2061 AN: 2116

Alfa AF: 0.980 Hom.: 110440

Bravo AF: 0.966

Asia WGS AF: 0.991 AC: 3441 AN: 3472

EpiCase AF: 0.984

EpiControl AF: 0.983

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:4

-

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

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

May 04, 2015

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Peters plus syndrome Benign:4

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. -

Aug 11, 2021

Fulgent Genetics, Fulgent Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.8
DANN	Benign	0.47
PhyloP100		-0.31
Mutation Taster		=70/30	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00057
dbscSNV1_RF	Benign	0.060
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

Other links and lift over

dbSNP: rs4943266; hg19: chr13-31821992;