rs786200938

Positions:

• chr1-1232279-A-C
• chr1-1232279-A-G

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1 PS1_Moderate PM2

The NM_080605.4(B3GALT6):​c.1A>C​(p.Met1?) variant causes a start lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000048 in 834,202 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: B3GALT6 NM_080605.4 start_lost
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.03

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 Pathogenic. Variant got 12 ACMG points.

• PVS1: Start lost variant, no new inframe start found.
• PS1: Another start lost variant in NM_080605.4 (B3GALT6) was described as [Pathogenic] in ClinVar as 60484
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
B3GALT6	NM_080605.4	c.1A>C	p.Met1?	start_lost	1/1	ENST00000379198.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
B3GALT6	ENST00000379198.5	c.1A>C	p.Met1?	start_lost	1/1		NM_080605.4	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000479 AC: 4 AN: 834202 Hom.: 0 Cov.: 29 AF XY: 0.00000259 AC XY: 1 AN XY: 385392

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: 0.00000393

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.057	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	20
DANN	Benign	0.66
DEOGEN2	Benign	0.0027	T;T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.48
FATHMM_MKL	Pathogenic	0.97	D
M_CAP	Pathogenic	0.96	D
MetaRNN	Pathogenic	0.80	D;D
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	D
Polyphen		0.0	B;B
Vest4		0.71
MutPred		0.85		Loss of catalytic residue at M1 (P = 0.1551);Loss of catalytic residue at M1 (P = 0.1551);
MVP		0.56
ClinPred		0.98	D
GERP RS		2.6
Varity_R		0.95
gMVP		0.57

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: rs786200938; hg19: chr1-1167659;