NM_194318.4:c.17G>A

Variant names:

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_194318.4(B3GLCT):c.17G>A(p.Cys6Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000574 in 1,375,972 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000060 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000057 ( 0 hom. )

Consequence

B3GLCT
NM_194318.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.742

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06580266).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
B3GLCT	NM_194318.4 link	c.17G>A	p.Cys6Tyr	missense_variant	Exon 1 of 15	ENST00000343307.5	NP_919299.3	Q6Y288
B3GLCT	XM_011534936.2 link	c.17G>A	p.Cys6Tyr	missense_variant	Exon 1 of 14		XP_011533238.1
B3GLCT	XM_047430111.1 link	c.17G>A	p.Cys6Tyr	missense_variant	Exon 1 of 12		XP_047286067.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
B3GLCT	ENST00000343307.5 link	c.17G>A	p.Cys6Tyr	missense_variant	Exon 1 of 15	1	NM_194318.4	ENSP00000343002.4		Q6Y288

Frequencies

GnomAD3 genomes

AF:

0.0000598

AC:

AN:

150572

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.000134

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000536

AC:

AN:

74664

Hom.:

AF XY:

0.0000466

AC XY:

AN XY:

42940

show subpopulations

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000149

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000571

AC:

AN:

1225400

Hom.:

Cov.:

AF XY:

0.0000480

AC XY:

AN XY:

603722

show subpopulations

Gnomad4 AFR exome

AF:

0.0000811

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000688

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000598

AC:

AN:

150572

Hom.:

Cov.:

AF XY:

0.0000544

AC XY:

AN XY:

73476

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000134

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000642

ExAC

AF:

0.0000229

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Peters plus syndrome

Uncertain:1

Jun 19, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 1504258). This variant has not been reported in the literature in individuals affected with B3GLCT-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 6 of the B3GLCT protein (p.Cys6Tyr). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.017

BayesDel_noAF

Benign

-0.26

CADD

Benign

DANN

Benign

0.90

DEOGEN2

Benign

0.048

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.78

FATHMM_MKL

Benign

0.043

LIST_S2

Benign

0.44

M_CAP

Benign

0.019

MetaRNN

Benign

0.066

MetaSVM

Benign

-0.89

MutationAssessor

Benign

0.0

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-0.48

REVEL

Benign

0.14

Sift

Pathogenic

0.0

Polyphen

0.0

Vest4

0.25

MutPred

0.58

Loss of catalytic residue at W7 (P = 0.0076);

MVP

0.49

MPC

0.37

ClinPred

0.30

GERP RS

2.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.51

gMVP

0.31

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over