rs4762896

Positions:

• chr12-22248977-C-T

Variant summary

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

The NM_003034.4(ST8SIA1):​c.584+29G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 1,527,574 control chromosomes in the GnomAD database, including 39,008 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 0.22 (3701 hom., cov: 32)
  • Exomes 𝑓: 0.22 (35307 hom.)
• Consequence: ST8SIA1 NM_003034.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0440

Genes affected

ST8SIA1 (HGNC:10869): (ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 1) Gangliosides are membrane-bound glycosphingolipids containing sialic acid. Ganglioside GD3 is known to be important for cell adhesion and growth of cultured malignant cells. The protein encoded by this gene is a type II membrane protein that catalyzes the transfer of sialic acid from CMP-sialic acid to GM3 to produce gangliosides GD3 and GT3. The encoded protein may be found in the Golgi apparatus and is a member of glycosyltransferase family 29. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jan 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.254 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ST8SIA1	NM_003034.4	c.584+29G>A		intron_variant		ENST00000396037.9	NP_003025.1
ST8SIA1	NM_001304450.2	c.155+29G>A		intron_variant			NP_001291379.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ST8SIA1	ENST00000396037.9	c.584+29G>A		intron_variant		1	NM_003034.4	ENSP00000379353	P1

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32700 AN: 151878 Hom.: 3696 Cov.: 32

Gnomad AFR AF: 0.202

Gnomad AMI AF: 0.201

Gnomad AMR AF: 0.261

Gnomad ASJ AF: 0.301

Gnomad EAS AF: 0.0620

Gnomad SAS AF: 0.191

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.309

Gnomad NFE AF: 0.234

Gnomad OTH AF: 0.244

GnomAD3 exomes AF: 0.209 AC: 51345 AN: 246026 Hom.: 5905 AF XY: 0.212 AC XY: 28100 AN XY: 132740

Gnomad AFR exome AF: 0.202

Gnomad AMR exome AF: 0.226

Gnomad ASJ exome AF: 0.307

Gnomad EAS exome AF: 0.0517

Gnomad SAS exome AF: 0.203

Gnomad FIN exome AF: 0.134

Gnomad NFE exome AF: 0.236

Gnomad OTH exome AF: 0.237

GnomAD4 exome AF: 0.222 AC: 305235 AN: 1375572 Hom.: 35307 Cov.: 21 AF XY: 0.223 AC XY: 153626 AN XY: 688972

Gnomad4 AFR exome AF: 0.205

Gnomad4 AMR exome AF: 0.227

Gnomad4 ASJ exome AF: 0.305

Gnomad4 EAS exome AF: 0.0747

Gnomad4 SAS exome AF: 0.201

Gnomad4 FIN exome AF: 0.141

Gnomad4 NFE exome AF: 0.230

Gnomad4 OTH exome AF: 0.232

GnomAD4 genome AF: 0.215 AC: 32713 AN: 152002 Hom.: 3701 Cov.: 32 AF XY: 0.209 AC XY: 15528 AN XY: 74288

Gnomad4 AFR AF: 0.202

Gnomad4 AMR AF: 0.260

Gnomad4 ASJ AF: 0.301

Gnomad4 EAS AF: 0.0615

Gnomad4 SAS AF: 0.191

Gnomad4 FIN AF: 0.131

Gnomad4 NFE AF: 0.234

Gnomad4 OTH AF: 0.247

Alfa AF: 0.242 Hom.: 4879

Bravo AF: 0.225

Asia WGS AF: 0.155 AC: 540 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.9
DANN	Benign	0.74

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: rs4762896; hg19: chr12-22401911; COSMIC: COSV53954792;