1-1232289-T-TGCGGCGGGCGTG

Variant names:

• chr1-1232289-T-TGCGGCGGGCGTG
• rs1553151150
• NM_080605.4:c.19_30dupGCGTGGCGGCGG

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP3

The NM_080605.4(B3GALT6):​c.19_30dupGCGTGGCGGCGG​(p.Ala7_Arg10dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000469 in 981,018 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.000028 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000050 (0 hom.)
• Consequence: B3GALT6 NM_080605.4 conservative_inframe_insertion
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:3
• Conservation: PhyloP100: -0.871

Genes affected

B3GALT6 (HGNC:17978): (beta-1,3-galactosyltransferase 6) The enzyme encoded by this intronless gene is a beta-1,3-galactosyltransferase found in the medial Golgi apparatus, where it catalyzes the transfer of galactose from UDP-galactose to substrates containing a terminal beta-linked galactose moiety. The encoded enzyme has a particular affinity for galactose-beta-1,4-xylose found in the linker region of glycosamines. This enzyme is required for glycosaminoglycan synthesis. [provided by RefSeq, Jun 2013]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP3: Nonframeshift variant in repetitive region in NM_080605.4

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
B3GALT6	NM_080605.4	c.19_30dupGCGTGGCGGCGG	p.Ala7_Arg10dup	conservative_inframe_insertion	Exon 1 of 1	ENST00000379198.5	NP_542172.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
B3GALT6	ENST00000379198.5	c.19_30dupGCGTGGCGGCGG	p.Ala7_Arg10dup	conservative_inframe_insertion	Exon 1 of 1	6	NM_080605.4	ENSP00000368496.2

Frequencies

GnomAD3 genomes AF: 0.0000275 AC: 4 AN: 145426 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000987

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000503 AC: 42 AN: 835592 Hom.: 0 Cov.: 29 AF XY: 0.0000492 AC XY: 19 AN XY: 386100

Gnomad4 AFR exome AF: 0.0000633

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: 0.0000524

Gnomad4 OTH exome AF: 0.0000365

GnomAD4 genome AF: 0.0000275 AC: 4 AN: 145426 Hom.: 0 Cov.: 32 AF XY: 0.0000424 AC XY: 3 AN XY: 70778

Gnomad4 AFR AF: 0.0000987

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: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Uncertain:2

Apr 13, 2017

GeneDx

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.19_30dup12 variant of uncertain significance in the B3GALT6 gene has not been published as pathogenic or been reported as benign to our knowledge. Data from control individuals was not available to assess whether c.19_30dup12 may be a common benign variant in the general population. (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). This variant results in an in-frame duplication of four amino acid residues starting at alanine 7 and extending through arginine 10, denoted p.Ala7_Arg10dupAlaTrpArgArg. While this variant alters the protein length, no truncated protein product or loss of protein through nonsense-mediated mRNA decay is predicted. Nevertheless, two other downstream in-frame insertion/deletion variants in the B3GALT6 gene have been reported in HGMD in association with spEDS (Stenson et al., 2014). -

Aug 01, 2019

CeGaT Center for Human Genetics Tuebingen

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Spondyloepimetaphyseal dysplasia with joint laxity;C3809210:Ehlers-Danlos syndrome, spondylodysplastic type, 2 Uncertain:1

Oct 13, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant, c.19_30dup, results in the insertion of 4 amino acid(s) of the B3GALT6 protein (p.Ala7_Arg10dup), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (no rsID available, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with B3GALT6-related conditions. ClinVar contains an entry for this variant (Variation ID: 426491). 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. -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1553151150; hg19: chr1-1167669;