rs2268861

Positions:

• chr12-22236540-G-A
• chr12-22236540-G-C
• chr12-22236540-G-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+12466C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 152,018 control chromosomes in the GnomAD database, including 9,318 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 0.33 (9318 hom., cov: 32)
• Consequence: ST8SIA1 NM_003034.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.441

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.526 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ST8SIA1	NM_003034.4	c.584+12466C>T		intron_variant		ENST00000396037.9
ST8SIA1	NM_001304450.2	c.155+12466C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ST8SIA1	ENST00000396037.9	c.584+12466C>T		intron_variant		1	NM_003034.4	P1

Frequencies

GnomAD3 genomes AF: 0.335 AC: 50882 AN: 151902 Hom.: 9313 Cov.: 32

Gnomad AFR AF: 0.229

Gnomad AMI AF: 0.507

Gnomad AMR AF: 0.427

Gnomad ASJ AF: 0.276

Gnomad EAS AF: 0.543

Gnomad SAS AF: 0.439

Gnomad FIN AF: 0.465

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.337

Gnomad OTH AF: 0.311

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.335 AC: 50903 AN: 152018 Hom.: 9318 Cov.: 32 AF XY: 0.346 AC XY: 25721 AN XY: 74320

Gnomad4 AFR AF: 0.229

Gnomad4 AMR AF: 0.428

Gnomad4 ASJ AF: 0.276

Gnomad4 EAS AF: 0.543

Gnomad4 SAS AF: 0.438

Gnomad4 FIN AF: 0.465

Gnomad4 NFE AF: 0.337

Gnomad4 OTH AF: 0.311

Alfa AF: 0.332 Hom.: 17882

Bravo AF: 0.327

Asia WGS AF: 0.477 AC: 1654 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	7.3
DANN	Benign	0.78

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: rs2268861; hg19: chr12-22389474;