12-22236540-G-A

Variant names:

• chr12-22236540-G-A
• rs2268861
• NM_003034.4:c.584+12466C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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=-0.89).
• 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 rank	MANE	Protein	UniProt
ST8SIA1	NM_003034.4	c.584+12466C>T		intron_variant	Intron 4 of 4	ENST00000396037.9	NP_003025.1
ST8SIA1	NM_001304450.2	c.155+12466C>T		intron_variant	Intron 3 of 3		NP_001291379.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ST8SIA1	ENST00000396037.9	c.584+12466C>T		intron_variant	Intron 4 of 4	1	NM_003034.4	ENSP00000379353.3

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

African (AFR) AF: 0.229 AC: 9504 AN: 41480

American (AMR) AF: 0.428 AC: 6534 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.276 AC: 955 AN: 3466

East Asian (EAS) AF: 0.543 AC: 2796 AN: 5150

South Asian (SAS) AF: 0.438 AC: 2108 AN: 4814

European-Finnish (FIN) AF: 0.465 AC: 4907 AN: 10562

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.337 AC: 22909 AN: 67964

Other (OTH) AF: 0.311 AC: 653 AN: 2102

Alfa AF: 0.334 Hom.: 37681

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
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: rs2268861; hg19: chr12-22389474;