3-187006156-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_173216.2(ST6GAL1):c.-182-32586A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0786 in 152,236 control chromosomes in the GnomAD database, including 545 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.079 (545 hom., cov: 31)
  • Exomes 𝑓: 0.083 (0 hom.)
• Consequence: ST6GAL1 NM_173216.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.283

Genes affected

ST6GAL1 (HGNC:10860): (ST6 beta-galactoside alpha-2,6-sialyltransferase 1) This gene encodes a member of glycosyltransferase family 29. The encoded protein is a type II membrane protein that catalyzes the transfer of sialic acid from CMP-sialic acid to galactose-containing substrates. The protein, which is normally found in the Golgi but can be proteolytically processed to a soluble form, is involved in the generation of the cell-surface carbohydrate determinants and differentiation antigens HB-6, CD75, and CD76. This gene has been incorrectly referred to as CD75. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.124 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ST6GAL1	NM_173216.2	c.-182-32586A>G		intron_variant		ENST00000169298.8
ST6GAL1	NM_173217.2	c.-218-32586A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ST6GAL1	ENST00000169298.8	c.-182-32586A>G		intron_variant		1	NM_173216.2	P1

Frequencies

GnomAD3 genomes AF: 0.0786 AC: 11960 AN: 152094 Hom.: 544 Cov.: 31

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.0647

Gnomad ASJ AF: 0.120

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0128

Gnomad FIN AF: 0.0443

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.0651

Gnomad OTH AF: 0.0996

GnomAD4 exome AF: 0.0833 AC: 2 AN: 24 Hom.: 0 Cov.: 0 AF XY: 0.100 AC XY: 2 AN XY: 20

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.125

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0786 AC: 11963 AN: 152212 Hom.: 545 Cov.: 31 AF XY: 0.0752 AC XY: 5596 AN XY: 74410

Gnomad4 AFR AF: 0.127

Gnomad4 AMR AF: 0.0646

Gnomad4 ASJ AF: 0.120

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0128

Gnomad4 FIN AF: 0.0443

Gnomad4 NFE AF: 0.0651

Gnomad4 OTH AF: 0.0981

Alfa AF: 0.0723 Hom.: 157

Bravo AF: 0.0860

Asia WGS AF: 0.0190 AC: 67 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	5.4
Dann	Benign	0.61

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: rs16861460; hg19: chr3-186723944;