11-62615724-A-G

Position:

• chr11-62615724-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_012200.4(B3GAT3):​c.985T>C​(p.Ser329Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: B3GAT3 NM_012200.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.64

Genes affected

B3GAT3 (HGNC:923): (beta-1,3-glucuronyltransferase 3) The protein encoded by this gene is a member of the glucuronyltransferase gene family, enzymes that exhibit strict acceptor specificity, recognizing nonreducing terminal sugars and their anomeric linkages. This gene product catalyzes the formation of the glycosaminoglycan-protein linkage by way of a glucuronyl transfer reaction in the final step of the biosynthesis of the linkage region of proteoglycans. A pseudogene of this gene has been identified on chromosome 3. [provided by RefSeq, Dec 2013]

B3GAT3 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
B3GAT3	NM_012200.4	c.985T>C	p.Ser329Pro	missense_variant	5/5	ENST00000265471.10	NP_036332.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
B3GAT3	ENST00000265471.10	c.985T>C	p.Ser329Pro	missense_variant	5/5	1	NM_012200.4	ENSP00000265471.5
B3GAT3	ENST00000532585.5	n.*1107T>C		non_coding_transcript_exon_variant	6/6	1		ENSP00000432604.1
B3GAT3	ENST00000532585.5	n.*1107T>C		3_prime_UTR_variant	6/6	1		ENSP00000432604.1
B3GAT3	ENST00000531383	c.*462T>C		3_prime_UTR_variant	5/5	2		ENSP00000431359.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Larsen-like syndrome, B3GAT3 type Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Aug 01, 2023

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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. This variant has not been reported in the literature in individuals affected with B3GAT3-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 329 of the B3GAT3 protein (p.Ser329Pro). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.87
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	T
Eigen	Pathogenic	0.69
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.88	D
M_CAP	Uncertain	0.17	D
MetaRNN	Uncertain	0.49	T
MetaSVM	Uncertain	0.27	D
MutationAssessor	Uncertain	2.6	M
PrimateAI	Uncertain	0.52	T
PROVEAN	Uncertain	-3.1	D
REVEL	Uncertain	0.52
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.41
MutPred		0.19		Loss of phosphorylation at S329 (P = 0.0062);
MVP		0.96
MPC		1.1
ClinPred		0.97	D
GERP RS		4.8
Varity_R		0.92
gMVP		0.57

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-62383196;