12-22294060-C-T

Variant names:

• chr12-22294060-C-T
• rs2160536
• NM_003034.4:c.237-6767G>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.237-6767G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.6 in 151,794 control chromosomes in the GnomAD database, including 28,304 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 0.60 (28304 hom., cov: 31)
• Consequence: ST8SIA1 NM_003034.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.38
• 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.751 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ST8SIA1	NM_003034.4	MANE Select	c.237-6767G>A		intron	N/A	NP_003025.1	Q92185-1
	ST8SIA1	NM_001304450.2		c.-83-6767G>A		intron	N/A	NP_001291379.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ST8SIA1	ENST00000396037.9	TSL:1 MANE Select	c.237-6767G>A		intron	N/A	ENSP00000379353.3	Q92185-1
	ST8SIA1	ENST00000261197.7	TSL:1	n.237-6767G>A		intron	N/A	ENSP00000261197.3	Q92185-2
	ST8SIA1	ENST00000859896.1		c.236+39937G>A		intron	N/A	ENSP00000529955.1

Frequencies

GnomAD3 genomes AF: 0.600 AC: 91051 AN: 151676 Hom.: 28265 Cov.: 31

Gnomad AFR AF: 0.758

Gnomad AMI AF: 0.674

Gnomad AMR AF: 0.502

Gnomad ASJ AF: 0.644

Gnomad EAS AF: 0.425

Gnomad SAS AF: 0.630

Gnomad FIN AF: 0.431

Gnomad MID AF: 0.741

Gnomad NFE AF: 0.560

Gnomad OTH AF: 0.598

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

GnomAD4 genome AF: 0.600 AC: 91135 AN: 151794 Hom.: 28304 Cov.: 31 AF XY: 0.593 AC XY: 44018 AN XY: 74170

African (AFR) AF: 0.758 AC: 31411 AN: 41414

American (AMR) AF: 0.501 AC: 7637 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.644 AC: 2233 AN: 3470

East Asian (EAS) AF: 0.424 AC: 2185 AN: 5150

South Asian (SAS) AF: 0.630 AC: 3022 AN: 4800

European-Finnish (FIN) AF: 0.431 AC: 4529 AN: 10498

Middle Eastern (MID) AF: 0.738 AC: 217 AN: 294

European-Non Finnish (NFE) AF: 0.560 AC: 38019 AN: 67910

Other (OTH) AF: 0.601 AC: 1269 AN: 2110

Alfa AF: 0.590 Hom.: 3462

Bravo AF: 0.607

Asia WGS AF: 0.544 AC: 1891 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.057
DANN	Benign	0.43
PhyloP100		-1.4
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: rs2160536; hg19: chr12-22446994;