Genetic Variant B3GALT6:p.Leu3Leu (chr1-1232285-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7

The NM_080605.4(B3GALT6):c.7C>T(p.Leu3Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000143 in 978,910 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 Likely benign (★★).

Frequency

Genomes: 𝑓 0.000021 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

B3GALT6
NM_080605.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.18

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 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 1-1232285-C-T is Benign according to our data. Variant chr1-1232285-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1254469.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.18 with no splicing effect.

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.7C>T	p.Leu3Leu	synonymous	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.7C>T	p.Leu3Leu	synonymous	Exon 1 of 1	ENSP00000368496.2	Q96L58
SDF4	ENST00000900948.1		c.-174-3339G>A		intron	N/A	ENSP00000571007.1
SDF4	ENST00000900949.1		c.-953G>A		upstream_gene	N/A	ENSP00000571008.1

Frequencies

GnomAD3 genomes

AF:

0.0000207

AC:

AN:

144738

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:

0.0000456

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000132

AC:

AN:

834172

Hom.:

Cov.:

AF XY:

0.0000104

AC XY:

AN XY:

385408

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

14952

American (AMR)

AF:

0.00

AC:

AN:

1044

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

5136

East Asian (EAS)

AF:

0.00

AC:

AN:

3648

South Asian (SAS)

AF:

0.00

AC:

AN:

17266

European-Finnish (FIN)

AF:

0.00

AC:

AN:

372

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1628

European-Non Finnish (NFE)

AF:

0.0000144

AC:

AN:

762822

Other (OTH)

AF:

0.00

AC:

AN:

27304

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

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:

0.0000207

AC:

AN:

144738

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

70422

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

39516

American (AMR)

AF:

0.00

AC:

AN:

14662

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3374

East Asian (EAS)

AF:

0.00

AC:

AN:

5066

South Asian (SAS)

AF:

0.00

AC:

AN:

4808

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8348

Middle Eastern (MID)

AF:

0.00

AC:

AN:

308

European-Non Finnish (NFE)

AF:

0.0000456

AC:

AN:

65756

Other (OTH)

AF:

0.00

AC:

AN:

1992

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000340

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

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

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

(source)

DANN

Benign

0.90

PhyloP100

1.2

PromoterAI

-0.014

Neutral

(source)

Mutation Taster

=98/2

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

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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