rs2216228

Variant names:

• chr12-22212901-T-C
• rs2216228
• NM_003034.4:c.585-10863A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003034.4(ST8SIA1):​c.585-10863A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 152,134 control chromosomes in the GnomAD database, including 3,816 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 0.21 (3816 hom., cov: 32)
• Consequence: ST8SIA1 NM_003034.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.705
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.317 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003034.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ST8SIA1	NM_003034.4	MANE Select	c.585-10863A>G		intron	N/A	NP_003025.1	Q92185-1
	ST8SIA1	NM_001304450.2		c.156-10863A>G		intron	N/A	NP_001291379.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ST8SIA1	ENST00000396037.9	TSL:1 MANE Select	c.585-10863A>G		intron	N/A	ENSP00000379353.3	Q92185-1
	ST8SIA1	ENST00000261197.7	TSL:1	n.*67-10863A>G		intron	N/A	ENSP00000261197.3	Q92185-2
	ST8SIA1	ENST00000859896.1		c.330-10863A>G		intron	N/A	ENSP00000529955.1

Frequencies

GnomAD3 genomes AF: 0.213 AC: 32361 AN: 152016 Hom.: 3812 Cov.: 32

Gnomad AFR AF: 0.283

Gnomad AMI AF: 0.113

Gnomad AMR AF: 0.217

Gnomad ASJ AF: 0.256

Gnomad EAS AF: 0.186

Gnomad SAS AF: 0.331

Gnomad FIN AF: 0.106

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.177

Gnomad OTH AF: 0.239

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

GnomAD4 genome AF: 0.213 AC: 32389 AN: 152134 Hom.: 3816 Cov.: 32 AF XY: 0.212 AC XY: 15743 AN XY: 74382

African (AFR) AF: 0.283 AC: 11754 AN: 41478

American (AMR) AF: 0.217 AC: 3309 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.256 AC: 889 AN: 3470

East Asian (EAS) AF: 0.185 AC: 959 AN: 5170

South Asian (SAS) AF: 0.331 AC: 1596 AN: 4822

European-Finnish (FIN) AF: 0.106 AC: 1121 AN: 10596

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.177 AC: 12065 AN: 67994

Other (OTH) AF: 0.239 AC: 505 AN: 2114

Alfa AF: 0.195 Hom.: 9062

Bravo AF: 0.221

Asia WGS AF: 0.255 AC: 890 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.3
DANN	Benign	0.58
PhyloP100		-0.70
Mutation Taster		=100/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2216228;

hg19: chr12-22365835;