rs2193177

Variant names:

• chr12-22269744-A-T
• rs2193177
• NM_003034.4:c.382-14355T>A

Variant summary

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

The NM_003034.4(ST8SIA1):​c.382-14355T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 152,190 control chromosomes in the GnomAD database, including 1,868 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 0.15 (1868 hom., cov: 32)
• Consequence: ST8SIA1 NM_003034.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.437
• Publications: 1 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.186 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ST8SIA1	NM_003034.4	MANE Select	c.382-14355T>A		intron	N/A	NP_003025.1
	ST8SIA1	NM_001304450.2		c.62+17405T>A		intron	N/A	NP_001291379.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ST8SIA1	ENST00000396037.9	TSL:1 MANE Select	c.382-14355T>A		intron	N/A	ENSP00000379353.3
	ST8SIA1	ENST00000261197.7	TSL:1	n.381+17405T>A		intron	N/A	ENSP00000261197.3
	ST8SIA1	ENST00000540824.5	TSL:4	c.235-14355T>A		intron	N/A	ENSP00000441707.1

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23460 AN: 152072 Hom.: 1862 Cov.: 32

Gnomad AFR AF: 0.189

Gnomad AMI AF: 0.139

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.210

Gnomad EAS AF: 0.0512

Gnomad SAS AF: 0.0833

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.157

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

GnomAD4 genome AF: 0.154 AC: 23495 AN: 152190 Hom.: 1868 Cov.: 32 AF XY: 0.150 AC XY: 11198 AN XY: 74408

African (AFR) AF: 0.189 AC: 7858 AN: 41508

American (AMR) AF: 0.123 AC: 1885 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.210 AC: 727 AN: 3470

East Asian (EAS) AF: 0.0511 AC: 265 AN: 5182

South Asian (SAS) AF: 0.0844 AC: 407 AN: 4822

European-Finnish (FIN) AF: 0.124 AC: 1313 AN: 10608

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.155 AC: 10503 AN: 67974

Other (OTH) AF: 0.160 AC: 338 AN: 2114

Alfa AF: 0.153 Hom.: 258

Bravo AF: 0.157

Asia WGS AF: 0.0790 AC: 274 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.0
DANN	Benign	0.79
PhyloP100		0.44
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

Other links and lift over

dbSNP: rs2193177; hg19: chr12-22422678;