chr11-62615779-C-T

Position:

• chr11-62615779-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_012200.4(B3GAT3):​c.930G>A​(p.Arg310Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00219 in 1,613,944 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0015 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0023 (7 hom.)
• Consequence: B3GAT3 NM_012200.4 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.213

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 Benign. Variant got -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BP6: Variant 11-62615779-C-T is Benign according to our data. Variant chr11-62615779-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 774896.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-62615779-C-T is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=0.213 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00148 (225/152382) while in subpopulation NFE AF= 0.00241 (164/68034). AF 95% confidence interval is 0.00211. There are 0 homozygotes in gnomad4. There are 100 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
B3GAT3	NM_012200.4	c.930G>A	p.Arg310Arg	synonymous_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.930G>A	p.Arg310Arg	synonymous_variant	5/5	1	NM_012200.4	ENSP00000265471.5
B3GAT3	ENST00000532585.5	n.*1052G>A		non_coding_transcript_exon_variant	6/6	1		ENSP00000432604.1
B3GAT3	ENST00000532585.5	n.*1052G>A		3_prime_UTR_variant	6/6	1		ENSP00000432604.1
B3GAT3	ENST00000531383	c.*407G>A		3_prime_UTR_variant	5/5	2		ENSP00000431359.1

Frequencies

GnomAD3 genomes AF: 0.00148 AC: 225 AN: 152264 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000555

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00183

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00241

Gnomad OTH AF: 0.00144

GnomAD3 exomes AF: 0.00145 AC: 364 AN: 250242 Hom.: 0 AF XY: 0.00146 AC XY: 197 AN XY: 135394

Gnomad AFR exome AF: 0.000370

Gnomad AMR exome AF: 0.00179

Gnomad ASJ exome AF: 0.000795

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000915

Gnomad FIN exome AF: 0.000609

Gnomad NFE exome AF: 0.00209

Gnomad OTH exome AF: 0.00179

GnomAD4 exome AF: 0.00226 AC: 3307 AN: 1461562 Hom.: 7 Cov.: 31 AF XY: 0.00219 AC XY: 1589 AN XY: 727090

Gnomad4 AFR exome AF: 0.000329

Gnomad4 AMR exome AF: 0.00168

Gnomad4 ASJ exome AF: 0.000727

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000649

Gnomad4 FIN exome AF: 0.000452

Gnomad4 NFE exome AF: 0.00268

Gnomad4 OTH exome AF: 0.00238

GnomAD4 genome AF: 0.00148 AC: 225 AN: 152382 Hom.: 0 Cov.: 33 AF XY: 0.00134 AC XY: 100 AN XY: 74520

Gnomad4 AFR AF: 0.000553

Gnomad4 AMR AF: 0.00183

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000828

Gnomad4 FIN AF: 0.000188

Gnomad4 NFE AF: 0.00241

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00196 Hom.: 1

Bravo AF: 0.00171

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00224

EpiControl AF: 0.00154

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 02, 2020	- -

Larsen-like syndrome, B3GAT3 type Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	9.2
DANN	Benign	0.79
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs147883248; hg19: chr11-62383251;