rs190796582

chr1-1232416-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_080605.4(B3GALT6):c.138C>T(p.Ser46=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 990,228 control chromosomes in the GnomAD database, including 8,160 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (2075 hom., cov: 33)
  • Exomes 𝑓: 0.12 (6085 hom.)
• Consequence: B3GALT6 NM_080605.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.620

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 Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 1-1232416-C-T is Benign according to our data. Variant chr1-1232416-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 193478.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.62 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.258 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
B3GALT6	NM_080605.4	c.138C>T	p.Ser46=	synonymous_variant	1/1	ENST00000379198.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
B3GALT6	ENST00000379198.5	c.138C>T	p.Ser46=	synonymous_variant	1/1		NM_080605.4	P1

Frequencies

GnomAD3 genomes AF: 0.152 AC: 22172 AN: 146168 Hom.: 2050 Cov.: 33

Gnomad AFR AF: 0.261

Gnomad AMI AF: 0.0998

Gnomad AMR AF: 0.0857

Gnomad ASJ AF: 0.0825

Gnomad EAS AF: 0.172

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.106

Gnomad NFE AF: 0.110

Gnomad OTH AF: 0.133

GnomAD3 exomes AF: 0.0761 AC: 7 AN: 92 Hom.: 0 AF XY: 0.0938 AC XY: 6 AN XY: 64

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.125

Gnomad ASJ exome AF: 0.00

Gnomad NFE exome AF: 0.0857

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.117 AC: 98855 AN: 843954 Hom.: 6085 Cov.: 30 AF XY: 0.117 AC XY: 45720 AN XY: 391040

Gnomad4 AFR exome AF: 0.265

Gnomad4 AMR exome AF: 0.0909

Gnomad4 ASJ exome AF: 0.0761

Gnomad4 EAS exome AF: 0.178

Gnomad4 SAS exome AF: 0.103

Gnomad4 FIN exome AF: 0.135

Gnomad4 NFE exome AF: 0.114

Gnomad4 OTH exome AF: 0.126

GnomAD4 genome AF: 0.152 AC: 22230 AN: 146274 Hom.: 2075 Cov.: 33 AF XY: 0.153 AC XY: 10864 AN XY: 71186

Gnomad4 AFR AF: 0.262

Gnomad4 AMR AF: 0.0853

Gnomad4 ASJ AF: 0.0825

Gnomad4 EAS AF: 0.173

Gnomad4 SAS AF: 0.0998

Gnomad4 FIN AF: 0.117

Gnomad4 NFE AF: 0.110

Gnomad4 OTH AF: 0.131

Alfa AF: 0.138 Hom.: 211

Asia WGS AF: 0.130 AC: 269 AN: 2074

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Feb 10, 2015	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 29, 2016	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

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

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
Cadd	Benign	5.3
Dann	Benign	0.88
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.6

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

LitVar

Other links and lift over

dbSNP: rs190796582; hg19: chr1-1167796;