rs2193177

chr12-22269744-A-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.186 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ST8SIA1	NM_003034.4	c.382-14355T>A		intron_variant		ENST00000396037.9
ST8SIA1	NM_001304450.2	c.62+17405T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ST8SIA1	ENST00000396037.9	c.382-14355T>A		intron_variant		1	NM_003034.4	P1

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

Gnomad4 AFR AF: 0.189

Gnomad4 AMR AF: 0.123

Gnomad4 ASJ AF: 0.210

Gnomad4 EAS AF: 0.0511

Gnomad4 SAS AF: 0.0844

Gnomad4 FIN AF: 0.124

Gnomad4 NFE AF: 0.155

Gnomad4 OTH AF: 0.160

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	5.0
Dann	Benign	0.79

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: rs2193177; hg19: chr12-22422678;