chr1-1232304-G-T

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 3P and 1B. PM2PP2BP4

The NM_080605.4(B3GALT6):c.26G>T(p.Arg9Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000397 in 982,428 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

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

Exomes 𝑓: 0.000045 ( 0 hom. )

Consequence

B3GALT6
NM_080605.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.95

Publications

1 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 links:

SDF4 (HGNC:24188): (stromal cell derived factor 4) This gene encodes a stromal cell derived factor that is a member of the CREC protein family. The encoded protein contains six EF-hand motifs and calcium-binding motifs. This protein localizes to the Golgi lumen and may be involved in regulating calcium dependent cellular activities. [provided by RefSeq, Sep 2011]

SDF4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 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=0.2942956).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080605.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	B3GALT6	NM_080605.4	MANE Select	c.26G>T	p.Arg9Leu	missense	Exon 1 of 1	NP_542172.2	Q96L58

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
B3GALT6	ENST00000379198.5	TSL:6 MANE Select	c.26G>T	p.Arg9Leu	missense	Exon 1 of 1	ENSP00000368496.2	Q96L58
SDF4	ENST00000900948.1		c.-174-3358C>A		intron	N/A	ENSP00000571007.1
SDF4	ENST00000900949.1		c.-972C>A		upstream_gene	N/A	ENSP00000571008.1

Frequencies

GnomAD3 genomes

AF:

0.00000684

AC:

AN:

146170

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

AF:

0.0000454

AC:

AN:

836258

Hom.:

Cov.:

AF XY:

0.0000310

AC XY:

AN XY:

386502

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

15814

American (AMR)

AF:

0.00

AC:

AN:

1070

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

5210

East Asian (EAS)

AF:

0.00

AC:

AN:

3684

South Asian (SAS)

AF:

0.00

AC:

AN:

17290

European-Finnish (FIN)

AF:

0.00

AC:

AN:

438

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1630

European-Non Finnish (NFE)

AF:

0.0000498

AC:

AN:

763688

Other (OTH)

AF:

0.00

AC:

AN:

27434

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.00000684

AC:

AN:

146170

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

71090

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

40816

American (AMR)

AF:

0.00

AC:

AN:

14710

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3392

East Asian (EAS)

AF:

0.00

AC:

AN:

5086

South Asian (SAS)

AF:

0.00

AC:

AN:

4808

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8344

Middle Eastern (MID)

AF:

0.00

AC:

AN:

308

European-Non Finnish (NFE)

AF:

0.0000152

AC:

AN:

65788

Other (OTH)

AF:

0.00

AC:

AN:

2008

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

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

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

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

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.093

BayesDel_noAF

Benign

-0.37

CADD

Uncertain

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0050

Eigen

Benign

-0.38

Eigen_PC

Benign

-0.26

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.52

M_CAP

Pathogenic

0.80

MetaRNN

Benign

0.29

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

PhyloP100

2.9

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

-0.81

REVEL

Benign

0.083

Sift

Pathogenic

0.0

Sift4G

Benign

0.16

Polyphen

0.0030

Vest4

0.38

MutPred

0.46

Loss of disorder (P = 0.0428)

MVP

0.60

MPC

1.1

ClinPred

0.90

GERP RS

3.1

PromoterAI

0.028

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.0

Varity_R

0.61

gMVP

0.57

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over