rs533071750

Variant names:

• chr1-1232859-CGGGG-C
• rs533071750
• NM_080605.4:c.585_588delGGGG

Your query was ambiguous. Multiple possible variants found:

• chr1-1232859-CGGGG-C
• chr1-1232859-CGGGG-CGGG
• chr1-1232859-CGGGG-CGGGGG

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PVS1_Strong PM2

The NM_080605.4(B3GALT6):​c.585_588delGGGG​(p.Gly196AlafsTer81) variant causes a frameshift change. The variant allele was found at a frequency of 0.000000724 in 1,381,436 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. G195G) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: B3GALT6 NM_080605.4 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.42
• Publications: 6 publications found

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]

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]

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. There are 16 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	B3GALT6	NM_080605.4	MANE Select	c.585_588delGGGG	p.Gly196AlafsTer81	frameshift	Exon 1 of 1	NP_542172.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	B3GALT6	ENST00000379198.5	TSL:6 MANE Select	c.585_588delGGGG	p.Gly196AlafsTer81	frameshift	Exon 1 of 1	ENSP00000368496.2
	SDF4	ENST00000900948.1		c.-174-3917_-174-3914delCCCC		intron	N/A	ENSP00000571007.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.24e-7 AC: 1 AN: 1381436 Hom.: 0 AF XY: 0.00000146 AC XY: 1 AN XY: 684854

African (AFR) AF: 0.00 AC: 0 AN: 28740

American (AMR) AF: 0.00 AC: 0 AN: 34230

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23876

East Asian (EAS) AF: 0.00 AC: 0 AN: 34532

South Asian (SAS) AF: 0.00 AC: 0 AN: 77102

European-Finnish (FIN) AF: 0.0000285 AC: 1 AN: 35134

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4134

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1086354

Other (OTH) AF: 0.00 AC: 0 AN: 57334

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		6.4

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

Other links and lift over

dbSNP: rs533071750; hg19: chr1-1168239;