Variant rs397514717 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM2PM5BP4_Moderate

The NM_080605.4(B3GALT6):c.694C>G(p.Arg232Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000709 in 1,411,198 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R232C) has been classified as Likely pathogenic.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

B3GALT6
NM_080605.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.16

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PM5

Other missense variant is known to change same aminoacid residue: Variant chr1-1232972-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 60485.We mark this variant Likely_pathogenic, oryginal submissions are: {Uncertain_significance=1, Likely_pathogenic=1}.

BP4

Computational evidence support a benign effect (MetaRNN=0.12299737).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
B3GALT6	NM_080605.4 linkuse as main transcript	c.694C>G	p.Arg232Gly	missense_variant	1/1	ENST00000379198.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
B3GALT6	ENST00000379198.5 linkuse as main transcript	c.694C>G	p.Arg232Gly	missense_variant	1/1		NM_080605.4	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000594

AC:

AN:

168310

Hom.:

AF XY:

0.0000107

AC XY:

AN XY:

93694

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000140

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.09e-7

AC:

AN:

1411198

Hom.:

Cov.:

AF XY:

0.00000143

AC XY:

AN XY:

699482

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.14e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 12, 2021

The c.694C>G (p.R232G) alteration is located in exon 1 (coding exon 1) of the B3GALT6 gene. This alteration results from a C to G substitution at nucleotide position 694, causing the arginine (R) at amino acid position 232 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Benign

0.87

DEOGEN2

Benign

0.0076

T;T

Eigen

Benign

-0.41

Eigen_PC

Benign

-0.25

FATHMM_MKL

Benign

0.67

LIST_S2

Benign

0.65

.;T

M_CAP

Pathogenic

0.33

MetaRNN

Benign

0.12

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.53

N;N

MutationTaster

Benign

0.66

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-1.6

.;N

REVEL

Benign

0.15

Sift

Benign

0.41

.;T

Sift4G

Benign

0.38

.;T

Polyphen

0.0

B;B

Vest4

0.11

MutPred

0.55

Gain of methylation at R229 (P = 0.0446);Gain of methylation at R229 (P = 0.0446);

MVP

0.53

MPC

1.2

ClinPred

0.066

GERP RS

3.0

Varity_R

0.29

gMVP

0.54

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over