1-1232289-TGCGGCGGGCGTGGCG-TGCGGCGGGCGTGGCGGCGGCGGGCGTGGCG

Variant names:

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP3BP6_Very_StrongBS1BS2

The NM_080605.4(B3GALT6):c.22_36dupTGGCGGCGGCGGGCG(p.Trp8_Ala12dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00213 in 981,116 control chromosomes in the GnomAD database, including 25 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0091 ( 18 hom., cov: 32)

Exomes 𝑓: 0.00092 ( 7 hom. )

Consequence

B3GALT6
NM_080605.4 conservative_inframe_insertion

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.871

Publications

0 publications found

Variant links:

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]

B3GALT6 Gene-Disease associations (from GenCC):

Ehlers-Danlos syndrome, spondylodysplastic type, 2
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, Genomics England PanelApp
spondyloepimetaphyseal dysplasia with joint laxity, type 1, with or without fractures
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
spondyloepimetaphyseal dysplasia with joint laxity
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

B3GALT6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -17 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_080605.4

BP6

Variant 1-1232289-T-TGCGGCGGGCGTGGCG is Benign according to our data. Variant chr1-1232289-T-TGCGGCGGGCGTGGCG is described in ClinVar as Benign. ClinVar VariationId is 450224.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00911 (1325/145524) while in subpopulation AFR AF = 0.0297 (1206/40652). AF 95% confidence interval is 0.0283. There are 18 homozygotes in GnomAd4. There are 625 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 18 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
B3GALT6	NM_080605.4 link	c.22_36dupTGGCGGCGGCGGGCG	p.Trp8_Ala12dup	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 link	c.22_36dupTGGCGGCGGCGGGCG	p.Trp8_Ala12dup	conservative_inframe_insertion	Exon 1 of 1	6	NM_080605.4	ENSP00000368496.2

Frequencies

GnomAD3 genomes

AF:

0.00914

AC:

1329

AN:

145418

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0298

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00286

Gnomad ASJ

AF:

0.00354

Gnomad EAS

AF:

0.00461

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00654

Gnomad NFE

AF:

0.000290

Gnomad OTH

AF:

0.00958

GnomAD4 exome

AF:

0.000919

AC:

768

AN:

835592

Hom.:

Cov.:

AF XY:

0.000919

AC XY:

355

AN XY:

386100

show subpopulations

African (AFR)

AF:

0.0336

AC:

531

AN:

15804

American (AMR)

AF:

0.00285

AC:

AN:

1052

Ashkenazi Jewish (ASJ)

AF:

0.00597

AC:

AN:

5190

East Asian (EAS)

AF:

0.00218

AC:

AN:

3668

South Asian (SAS)

AF:

0.000752

AC:

AN:

17296

European-Finnish (FIN)

AF:

0.00

AC:

AN:

380

Middle Eastern (MID)

AF:

0.00123

AC:

AN:

1630

European-Non Finnish (NFE)

AF:

0.000159

AC:

121

AN:

763176

Other (OTH)

AF:

0.00215

AC:

AN:

27396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

148

197

246

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

128

160

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00911

AC:

1325

AN:

145524

Hom.:

Cov.:

AF XY:

0.00882

AC XY:

625

AN XY:

70892

show subpopulations

African (AFR)

AF:

0.0297

AC:

1206

AN:

40652

American (AMR)

AF:

0.00286

AC:

AN:

14694

Ashkenazi Jewish (ASJ)

AF:

0.00354

AC:

AN:

3386

East Asian (EAS)

AF:

0.00462

AC:

AN:

4978

South Asian (SAS)

AF:

0.00105

AC:

AN:

4782

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8314

Middle Eastern (MID)

AF:

0.00

AC:

AN:

284

European-Non Finnish (NFE)

AF:

0.000290

AC:

AN:

65526

Other (OTH)

AF:

0.00897

AC:

AN:

2006

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

121

182

242

303

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00137

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

May 17, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Dec 18, 2019

GeneDx

Significance:Likely benign

Review Status:flagged submission

Collection Method:clinical testing

- -

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

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.87

Mutation Taster

=86/14

polymorphism

(source)

Splicing

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over