rs397514719

Positions:

• chr1-1232471-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2 PP5 BP4

The NM_080605.4(B3GALT6):​c.193A>G​(p.Ser65Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000346 in 866,258 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000035 (0 hom.)
• Consequence: B3GALT6 NM_080605.4 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 2.09

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 1-1232471-A-G is Pathogenic according to our data. Variant chr1-1232471-A-G is described in ClinVar as [Pathogenic]. Clinvar id is 60488.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP4: Computational evidence support a benign effect (MetaRNN=0.42055872). . Strength limited to SUPPORTING due to the PP5.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
B3GALT6	NM_080605.4	c.193A>G	p.Ser65Gly	missense_variant	1/1	ENST00000379198.5	NP_542172.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
B3GALT6	ENST00000379198.5	c.193A>G	p.Ser65Gly	missense_variant	1/1		NM_080605.4	ENSP00000368496	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000346 AC: 3 AN: 866258 Hom.: 0 Cov.: 30 AF XY: 0.00000248 AC XY: 1 AN XY: 403256

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: 0.00000383

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Spondyloepimetaphyseal dysplasia with joint laxity, type 1, with or without fractures Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jun 06, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.45
BayesDel_addAF	Benign	-0.0055	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	21
DANN	Benign	0.94
DEOGEN2	Benign	0.41	T;T
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.081
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.44	.;T
M_CAP	Pathogenic	0.94	D
MetaRNN	Benign	0.42	T;T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	1.6	L;L
MutationTaster	Benign	1.0	D
PrimateAI	Pathogenic	0.93	D
PROVEAN	Uncertain	-3.3	.;D
REVEL	Benign	0.21
Sift	Uncertain	0.0030	.;D
Sift4G	Uncertain	0.0050	.;D
Polyphen		0.46	P;P
Vest4		0.69
MutPred		0.34		Loss of glycosylation at S65 (P = 0.0118);Loss of glycosylation at S65 (P = 0.0118);
MVP		0.71
MPC		1.0
ClinPred		0.90	D
GERP RS		3.5
Varity_R		0.77
gMVP		0.82

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: rs397514719; hg19: chr1-1167851;