chr12-22221888-A-G

Variant names:

• chr12-22221888-A-G
• rs2041906
• NM_003034.4:c.585-19850T>C

Variant summary

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

The NM_003034.4(ST8SIA1):​c.585-19850T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.545 in 151,908 control chromosomes in the GnomAD database, including 22,859 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 0.54 (22859 hom., cov: 32)
• Consequence: ST8SIA1 NM_003034.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0760
• Publications: 4 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.63 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.585-19850T>C		intron	N/A	NP_003025.1
	ST8SIA1	NM_001304450.2		c.156-19850T>C		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.585-19850T>C		intron	N/A	ENSP00000379353.3
	ST8SIA1	ENST00000261197.7	TSL:1	n.*67-19850T>C		intron	N/A	ENSP00000261197.3
	ST8SIA1	ENST00000540824.5	TSL:4	c.438-19850T>C		intron	N/A	ENSP00000441707.1

Frequencies

GnomAD3 genomes AF: 0.544 AC: 82641 AN: 151790 Hom.: 22831 Cov.: 32

Gnomad AFR AF: 0.444

Gnomad AMI AF: 0.786

Gnomad AMR AF: 0.558

Gnomad ASJ AF: 0.628

Gnomad EAS AF: 0.648

Gnomad SAS AF: 0.581

Gnomad FIN AF: 0.577

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.579

Gnomad OTH AF: 0.567

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

GnomAD4 genome AF: 0.545 AC: 82715 AN: 151908 Hom.: 22859 Cov.: 32 AF XY: 0.548 AC XY: 40688 AN XY: 74230

African (AFR) AF: 0.444 AC: 18402 AN: 41448

American (AMR) AF: 0.558 AC: 8513 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.628 AC: 2182 AN: 3472

East Asian (EAS) AF: 0.648 AC: 3339 AN: 5152

South Asian (SAS) AF: 0.581 AC: 2799 AN: 4814

European-Finnish (FIN) AF: 0.577 AC: 6067 AN: 10512

Middle Eastern (MID) AF: 0.612 AC: 180 AN: 294

European-Non Finnish (NFE) AF: 0.579 AC: 39318 AN: 67944

Other (OTH) AF: 0.569 AC: 1200 AN: 2108

Alfa AF: 0.574 Hom.: 28932

Bravo AF: 0.539

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	9.5
DANN	Benign	0.81
PhyloP100		0.076
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: rs2041906; hg19: chr12-22374822;