chr1-1232295-G-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 3P and 4B. PM2PP2BP4_Strong

The NM_080605.4(B3GALT6):c.17G>T(p.Arg6Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 146,176 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R6Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000068 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

B3GALT6
NM_080605.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.616

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: Likely_benign. The variant received -1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 12 curated pathogenic missense variants (we use a threshold of 10). The gene has 3 curated benign missense variants. Gene score misZ: 1.2608 (below the threshold of 3.09). Trascript score misZ: -4.8226 (below the threshold of 3.09). GenCC associations: The gene is linked to spondyloepimetaphyseal dysplasia with joint laxity, type 1, with or without fractures, Ehlers-Danlos syndrome, spondylodysplastic type, 2, spondyloepimetaphyseal dysplasia with joint laxity.

BP4

Computational evidence support a benign effect (MetaRNN=0.06699088).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
B3GALT6	NM_080605.4 link	c.17G>T	p.Arg6Leu	missense_variant	Exon 1 of 1	ENST00000379198.5	NP_542172.2	Q96L58

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
B3GALT6	ENST00000379198.5 link	c.17G>T	p.Arg6Leu	missense_variant	Exon 1 of 1	6	NM_080605.4	ENSP00000368496.2		Q96L58

Frequencies

GnomAD3 genomes

AF:

0.00000684

AC:

AN:

146176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000152

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

835800

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

386226

African (AFR)

AF:

0.00

AC:

AN:

15810

American (AMR)

AF:

0.00

AC:

AN:

1060

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

5198

East Asian (EAS)

AF:

0.00

AC:

AN:

3668

South Asian (SAS)

AF:

0.00

AC:

AN:

17282

European-Finnish (FIN)

AF:

0.00

AC:

AN:

406

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1630

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

763334

Other (OTH)

AF:

0.00

AC:

AN:

27412

GnomAD4 genome

AF:

0.00000684

AC:

AN:

146176

Hom.:

Cov.:

AF XY:

0.0000141

AC XY:

AN XY:

71116

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40812

American (AMR)

AF:

0.00

AC:

AN:

14714

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3394

East Asian (EAS)

AF:

0.00

AC:

AN:

5082

South Asian (SAS)

AF:

0.00

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8342

Middle Eastern (MID)

AF:

0.00

AC:

AN:

306

European-Non Finnish (NFE)

AF:

0.0000152

AC:

AN:

65780

Other (OTH)

AF:

0.00

AC:

AN:

2018

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.61

CADD

Benign

(source)

DANN

Benign

0.72

DEOGEN2

Benign

0.0040

T;T

Eigen

Benign

-0.95

Eigen_PC

Benign

-0.82

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.52

.;T

M_CAP

Pathogenic

0.50

MetaRNN

Benign

0.067

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

N;N

PhyloP100

0.62

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-0.24

.;N

REVEL

Benign

0.060

Sift

Benign

1.0

.;T

Sift4G

Benign

1.0

.;T

Polyphen

0.0

B;B

Vest4

0.064

MutPred

0.34

Gain of catalytic residue at R6 (P = 0.0116);Gain of catalytic residue at R6 (P = 0.0116);

MVP

0.42

MPC

1.1

ClinPred

0.077

GERP RS

2.5

PromoterAI

0.0028

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.0

Varity_R

0.18

gMVP

0.42

Mutation Taster

=66/34

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over