Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2PP2PP3_ModeratePP5

The ENST00000265471.10(B3GAT3):c.419C>T(p.Pro140Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 32)

Consequence

B3GAT3
ENST00000265471.10 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 5.63

Publications

6 publications found

Variant links:

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 Gene-Disease associations (from GenCC):

Larsen-like syndrome, B3GAT3 type
Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet, PanelApp Australia
complex neurodevelopmental disorder
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

B3GAT3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 8 curated pathogenic missense variants (we use a threshold of 10). The gene has 2 curated benign missense variants. Gene score misZ: 0.69161 (below the threshold of 3.09). Trascript score misZ: 1.8273 (below the threshold of 3.09). GenCC associations: The gene is linked to Larsen-like syndrome, B3GAT3 type, complex neurodevelopmental disorder.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.898

PP5

Variant 11-62617186-G-A is Pathogenic according to our data. Variant chr11-62617186-G-A is described in ClinVar as Pathogenic. ClinVar VariationId is 225764.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000265471.10. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
B3GAT3	NM_012200.4	MANE Select	c.419C>T	p.Pro140Leu	missense	Exon 3 of 5	NP_036332.2
B3GAT3	NM_001288721.2		c.398C>T	p.Pro133Leu	missense	Exon 4 of 6	NP_001275650.1
B3GAT3	NM_001288722.2		c.419C>T	p.Pro140Leu	missense	Exon 3 of 5	NP_001275651.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
B3GAT3	ENST00000265471.10	TSL:1 MANE Select	c.419C>T	p.Pro140Leu	missense	Exon 3 of 5	ENSP00000265471.5
B3GAT3	ENST00000532585.5	TSL:1	n.*541C>T		non_coding_transcript_exon	Exon 4 of 6	ENSP00000432604.1
B3GAT3	ENST00000532585.5	TSL:1	n.*541C>T		3_prime_UTR	Exon 4 of 6	ENSP00000432604.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions as Germline

Significance:Pathogenic

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

MULTIPLE JOINT DISLOCATIONS, SHORT STATURE, AND CRANIOFACIAL DYSMORPHISM WITHOUT CONGENITAL HEART DEFECTS (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.39

BayesDel_addAF

Uncertain

0.092

BayesDel_noAF

Benign

-0.11

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.38

Eigen

Pathogenic

0.73

Eigen_PC

Pathogenic

0.68

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.90

M_CAP

Uncertain

0.13

MetaRNN

Pathogenic

0.90

MetaSVM

Uncertain

0.45

MutationAssessor

Uncertain

2.7

PhyloP100

5.6

PrimateAI

Uncertain

0.74

PROVEAN

Pathogenic

-7.8

REVEL

Uncertain

0.53

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0020

Polyphen

0.77

Vest4

0.86

MutPred

0.73

Loss of disorder (P = 0.0736)

MVP

0.97

MPC

0.62

ClinPred

1.0

GERP RS

5.6

Varity_R

0.90

gMVP

0.80

Mutation Taster

=3/97

disease causing (ClinVar)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over