13-31317606-G-T

Variant names:

• chr13-31317606-G-T
• rs34638481
• NM_194318.4:c.1105G>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.1105G>T​(p.Gly369Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G369S) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: B3GLCT NM_194318.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.338
• Publications: 9 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=0.24470377).

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.1105G>T	p.Gly369Cys	missense	Exon 13 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.1105G>T	p.Gly369Cys	missense	Exon 13 of 15	ENSP00000343002.4	Q6Y288
	B3GLCT	ENST00000873566.1		c.916G>T	p.Gly306Cys	missense	Exon 11 of 13	ENSP00000543625.1
	B3GLCT	ENST00000946543.1		c.766G>T	p.Gly256Cys	missense	Exon 9 of 11	ENSP00000616602.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 269

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.051	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	5.9
DANN	Uncertain	0.98
DEOGEN2	Benign	0.078	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.046	N
LIST_S2	Benign	0.86	D
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-0.39	T
MutationAssessor	Benign	0.81	L
PhyloP100		0.34
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.1	N
REVEL	Uncertain	0.33
Sift	Uncertain	0.029	D
Sift4G	Uncertain	0.042	D
Polyphen		0.74	P
Vest4		0.39
MutPred		0.46		Loss of disorder (P = 0.0817)
MVP		0.42
MPC		0.66
ClinPred		0.36	T
GERP RS		-3.2
Varity_R		0.10
gMVP		0.50
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs34638481; hg19: chr13-31891743;