rs999173078

Variant names:

• chr13-31200140-T-C
• rs999173078
• NM_194318.4:c.56T>C

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_194318.4(B3GLCT):​c.56T>C​(p.Leu19Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000279 in 1,359,576 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.00017 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00029 (1 hom.)
• Consequence: B3GLCT NM_194318.4 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:3
• Conservation: PhyloP100: 0.535
• 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: Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp, Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.3689387).

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.56T>C	p.Leu19Pro	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.56T>C	p.Leu19Pro	missense	Exon 1 of 15	ENSP00000343002.4	Q6Y288
	B3GLCT	ENST00000873566.1		c.56T>C	p.Leu19Pro	missense	Exon 1 of 13	ENSP00000543625.1
	B3GLCT	ENST00000946543.1		c.56T>C	p.Leu19Pro	missense	Exon 1 of 11	ENSP00000616602.1

Frequencies

GnomAD3 genomes AF: 0.000173 AC: 26 AN: 150110 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000485

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.000357

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000127 AC: 9 AN: 70866 AF XY: 0.000170

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000348

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000292 AC: 353 AN: 1209466 Hom.: 1 Cov.: 30 AF XY: 0.000255 AC XY: 152 AN XY: 595222

African (AFR) AF: 0.0000826 AC: 2 AN: 24224

American (AMR) AF: 0.00 AC: 0 AN: 22026

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19356

East Asian (EAS) AF: 0.00 AC: 0 AN: 22754

South Asian (SAS) AF: 0.00 AC: 0 AN: 64130

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 27896

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3350

European-Non Finnish (NFE) AF: 0.000350 AC: 343 AN: 978640

Other (OTH) AF: 0.000170 AC: 8 AN: 47090

GnomAD4 genome AF: 0.000173 AC: 26 AN: 150110 Hom.: 0 Cov.: 32 AF XY: 0.000150 AC XY: 11 AN XY: 73248

African (AFR) AF: 0.0000485 AC: 2 AN: 41224

American (AMR) AF: 0.00 AC: 0 AN: 15112

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3448

East Asian (EAS) AF: 0.00 AC: 0 AN: 5128

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9852

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

European-Non Finnish (NFE) AF: 0.000357 AC: 24 AN: 67236

Other (OTH) AF: 0.00 AC: 0 AN: 2062

Alfa AF: 0.000427 Hom.: 0

Bravo AF: 0.000147

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	2	-	Peters plus syndrome (2)
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.16
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.058	T
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.034	N
LIST_S2	Benign	0.30	T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.37	T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	1.2	L
PhyloP100		0.54
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-0.78	N
REVEL	Benign	0.18
Sift	Benign	0.072	T
Sift4G	Benign	0.36	T
Polyphen		0.78	P
Vest4		0.52
MutPred		0.59		Loss of helix (P = 3e-04)
MVP		0.72
MPC		0.38
ClinPred		0.094	T
GERP RS		2.4
PromoterAI		0.070	Neutral
Varity_R		0.51
gMVP		0.48
Mutation Taster		=76/24	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: rs999173078; hg19: chr13-31774277;