rs2239612

chr3-187075454-G-A

Variant summary

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

The NM_173216.2(ST6GAL1):c.980-108G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 1,500,714 control chromosomes in the GnomAD database, including 14,309 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 0.17 (2658 hom., cov: 32)
  • Exomes 𝑓: 0.13 (11651 hom.)
• Consequence: ST6GAL1 NM_173216.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09

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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.272 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ST6GAL1	NM_173216.2	c.980-108G>A		intron_variant		ENST00000169298.8
ST6GAL1	NM_001353916.2	c.980-108G>A		intron_variant
ST6GAL1	NM_003032.3	c.980-108G>A		intron_variant
ST6GAL1	NM_173217.2	c.287-108G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ST6GAL1	ENST00000169298.8	c.980-108G>A		intron_variant		1	NM_173216.2	P1

Frequencies

GnomAD3 genomes AF: 0.172 AC: 26108 AN: 151992 Hom.: 2642 Cov.: 32

Gnomad AFR AF: 0.276

Gnomad AMI AF: 0.0822

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.0985

Gnomad EAS AF: 0.177

Gnomad SAS AF: 0.110

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.174

GnomAD4 exome AF: 0.125 AC: 168776 AN: 1348604 Hom.: 11651 AF XY: 0.124 AC XY: 82093 AN XY: 664670

Gnomad4 AFR exome AF: 0.289

Gnomad4 AMR exome AF: 0.263

Gnomad4 ASJ exome AF: 0.0972

Gnomad4 EAS exome AF: 0.186

Gnomad4 SAS exome AF: 0.102

Gnomad4 FIN exome AF: 0.139

Gnomad4 NFE exome AF: 0.114

Gnomad4 OTH exome AF: 0.135

GnomAD4 genome AF: 0.172 AC: 26157 AN: 152110 Hom.: 2658 Cov.: 32 AF XY: 0.172 AC XY: 12813 AN XY: 74372

Gnomad4 AFR AF: 0.277

Gnomad4 AMR AF: 0.206

Gnomad4 ASJ AF: 0.0985

Gnomad4 EAS AF: 0.176

Gnomad4 SAS AF: 0.110

Gnomad4 FIN AF: 0.136

Gnomad4 NFE AF: 0.115

Gnomad4 OTH AF: 0.176

Alfa AF: 0.128 Hom.: 931

Bravo AF: 0.187

Asia WGS AF: 0.171 AC: 594 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	0.41
Dann	Benign	0.50

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: rs2239612; hg19: chr3-186793242; COSMIC: COSV51471595; COSMIC: COSV51471595;