rs1868555206

Variant names:

• chr13-31200112-C-T
• rs1868555206
• NM_194318.4:c.28C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_194318.4(B3GLCT):​c.28C>T​(p.Leu10Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000665 in 150,424 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. L10L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: B3GLCT NM_194318.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.414
• Publications: 0 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: PanelApp Australia, Orphanet, G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.095202565).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_194318.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	B3GLCT	NM_194318.4	MANE Select	c.28C>T	p.Leu10Phe	missense	Exon 1 of 15	NP_919299.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	B3GLCT	ENST00000343307.5	TSL:1 MANE Select	c.28C>T	p.Leu10Phe	missense	Exon 1 of 15	ENSP00000343002.4	Q6Y288
	B3GLCT	ENST00000873566.1		c.28C>T	p.Leu10Phe	missense	Exon 1 of 13	ENSP00000543625.1
	B3GLCT	ENST00000946543.1		c.28C>T	p.Leu10Phe	missense	Exon 1 of 11	ENSP00000616602.1

Frequencies

GnomAD3 genomes AF: 0.00000665 AC: 1 AN: 150424 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000661

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1226030 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 603998

African (AFR) AF: 0.00 AC: 0 AN: 24628

American (AMR) AF: 0.00 AC: 0 AN: 23546

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19834

East Asian (EAS) AF: 0.00 AC: 0 AN: 23234

South Asian (SAS) AF: 0.00 AC: 0 AN: 66552

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28638

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3406

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 988102

Other (OTH) AF: 0.00 AC: 0 AN: 48090

GnomAD4 genome AF: 0.00000665 AC: 1 AN: 150424 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 73396

African (AFR) AF: 0.00 AC: 0 AN: 41272

American (AMR) AF: 0.0000661 AC: 1 AN: 15122

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3450

East Asian (EAS) AF: 0.00 AC: 0 AN: 5158

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9954

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67344

Other (OTH) AF: 0.00 AC: 0 AN: 2068

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Peters plus syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.021	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	12
DANN	Benign	0.94
DEOGEN2	Benign	0.047	T
Eigen	Benign	-0.87
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.044	N
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.067	D
MetaRNN	Benign	0.095	T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	0.34	N
PhyloP100		0.41
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-0.26	N
REVEL	Benign	0.15
Sift	Benign	0.072	T
Sift4G	Benign	0.13	T
Polyphen		0.11	B
Vest4		0.20
MutPred		0.20		Loss of helix (P = 0.1299)
MVP		0.40
MPC		0.32
ClinPred		0.12	T
GERP RS		2.0
PromoterAI		0.020	Neutral
Varity_R		0.055
gMVP		0.15
Mutation Taster		=78/22	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs1868555206; hg19: chr13-31774249;