12-22294060-C-T

Variant names:

• chr12-22294060-C-T
• rs2160536
• NM_003034.4:c.237-6767G>A

Variant summary

Our verdict is Benign. Variant got -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

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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.751 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ST8SIA1	NM_003034.4	c.237-6767G>A		intron_variant	Intron 1 of 4	ENST00000396037.9	NP_003025.1
ST8SIA1	NM_001304450.2	c.-83-6767G>A		intron_variant	Intron 1 of 3		NP_001291379.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ST8SIA1	ENST00000396037.9	c.237-6767G>A		intron_variant	Intron 1 of 4	1	NM_003034.4	ENSP00000379353.3
ST8SIA1	ENST00000261197.7	n.237-6767G>A		intron_variant	Intron 1 of 3	1		ENSP00000261197.3
ST8SIA1	ENST00000540824.5	c.90-6767G>A		intron_variant	Intron 1 of 4	4		ENSP00000441707.1
ST8SIA1	ENST00000541868.1	c.168-6767G>A		intron_variant	Intron 1 of 3	3		ENSP00000440292.1

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

Gnomad4 AFR AF: 0.758

Gnomad4 AMR AF: 0.501

Gnomad4 ASJ AF: 0.644

Gnomad4 EAS AF: 0.424

Gnomad4 SAS AF: 0.630

Gnomad4 FIN AF: 0.431

Gnomad4 NFE AF: 0.560

Gnomad4 OTH AF: 0.601

Alfa AF: 0.584 Hom.: 3249

Bravo AF: 0.607

Asia WGS AF: 0.544 AC: 1891 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.057
DANN	Benign	0.43

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: rs2160536; hg19: chr12-22446994;