11-62617050-CC-TT

Variant names:

• chr11-62617050-CC-TT
• NM_012200.4:c.554_555delGGinsAA
• B3GAT3 p.Gly185Glu

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP2

The NM_012200.4(B3GAT3):​c.554_555delGGinsAA​(p.Gly185Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: B3GAT3 NM_012200.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.53
• Publications: 0 publications found

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: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), Orphanet
• complex neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012200.4. 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
	B3GAT3	NM_012200.4	MANE Select	c.554_555delGGinsAA	p.Gly185Glu	missense	N/A	NP_036332.2
	B3GAT3	NM_001288721.2		c.533_534delGGinsAA	p.Gly178Glu	missense	N/A	NP_001275650.1
	B3GAT3	NM_001288722.2		c.554_555delGGinsAA	p.Gly185Glu	missense	N/A	NP_001275651.1	G3V150

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	B3GAT3	ENST00000265471.10	TSL:1 MANE Select	c.554_555delGGinsAA	p.Gly185Glu	missense	N/A	ENSP00000265471.5	O94766-1
	B3GAT3	ENST00000532585.5	TSL:1	n.*676_*677delGGinsAA		non_coding_transcript_exon	Exon 4 of 6	ENSP00000432604.1	E9PQ60
	B3GAT3	ENST00000532585.5	TSL:1	n.*676_*677delGGinsAA		3_prime_UTR	Exon 4 of 6	ENSP00000432604.1	E9PQ60

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.5

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr11-62384522;