15-92428581-T-G

Variant names:

• chr15-92428581-T-G
• rs3858917
• NM_006011.4:c.99-1468T>G

Variant summary

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

The NM_006011.4(ST8SIA2):​c.99-1468T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.431 in 152,012 control chromosomes in the GnomAD database, including 15,530 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 0.43 (15530 hom., cov: 32)
• Consequence: ST8SIA2 NM_006011.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.537
• Publications: 5 publications found

Genes affected

ST8SIA2 (HGNC:10870): (ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 2) The protein encoded by this gene is a type II membrane protein that is thought to catalyze the transfer of sialic acid from CMP-sialic acid to N-linked oligosaccharides and glycoproteins. The encoded protein may be found in the Golgi apparatus and may be involved in the production of polysialic acid, a modulator of the adhesive properties of neural cell adhesion molecule (NCAM1). This protein is a member of glycosyltransferase family 29. [provided by RefSeq, Jul 2008]

ST8SIA2 Gene-Disease associations (from GenCC):

• schizophrenia

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.681 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ST8SIA2	NM_006011.4	c.99-1468T>G		intron_variant	Intron 1 of 5	ENST00000268164.8	NP_006002.1
ST8SIA2	NM_001330416.2	c.99-5666T>G		intron_variant	Intron 1 of 4		NP_001317345.1
ST8SIA2	XM_017022642.2	c.162-1468T>G		intron_variant	Intron 1 of 5		XP_016878131.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ST8SIA2	ENST00000268164.8	c.99-1468T>G		intron_variant	Intron 1 of 5	1	NM_006011.4	ENSP00000268164.3
ST8SIA2	ENST00000539113.5	c.99-5666T>G		intron_variant	Intron 1 of 4	1		ENSP00000437382.1
ST8SIA2	ENST00000555434.1	c.99-1468T>G		intron_variant	Intron 1 of 4	5		ENSP00000450851.1

Frequencies

GnomAD3 genomes AF: 0.431 AC: 65470 AN: 151894 Hom.: 15527 Cov.: 32

Gnomad AFR AF: 0.231

Gnomad AMI AF: 0.362

Gnomad AMR AF: 0.526

Gnomad ASJ AF: 0.545

Gnomad EAS AF: 0.700

Gnomad SAS AF: 0.505

Gnomad FIN AF: 0.470

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.494

Gnomad OTH AF: 0.436

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

GnomAD4 genome AF: 0.431 AC: 65483 AN: 152012 Hom.: 15530 Cov.: 32 AF XY: 0.438 AC XY: 32517 AN XY: 74308

African (AFR) AF: 0.231 AC: 9562 AN: 41472

American (AMR) AF: 0.527 AC: 8043 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.545 AC: 1888 AN: 3464

East Asian (EAS) AF: 0.700 AC: 3614 AN: 5166

South Asian (SAS) AF: 0.505 AC: 2433 AN: 4814

European-Finnish (FIN) AF: 0.470 AC: 4966 AN: 10556

Middle Eastern (MID) AF: 0.480 AC: 141 AN: 294

European-Non Finnish (NFE) AF: 0.494 AC: 33594 AN: 67964

Other (OTH) AF: 0.432 AC: 913 AN: 2114

Alfa AF: 0.460 Hom.: 2117

Bravo AF: 0.425

Asia WGS AF: 0.539 AC: 1869 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.5
DANN	Benign	0.53
PhyloP100		0.54
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: rs3858917; hg19: chr15-92971811;