12-22077045-A-C

Variant names:

• chr12-22077045-A-C
• rs759582
• ENST00000544732.5:n.298-6420T>G

Variant summary

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

The XR_931423.4(LOC105369690):​n.142+5341T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.543 in 152,140 control chromosomes in the GnomAD database, including 23,699 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 (23699 hom., cov: 32)
• Consequence: LOC105369690 XR_931423.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.319
• Publications: 3 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]

LOC105369690 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.633 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105369690	XR_931423.4	n.142+5341T>G		intron_variant	Intron 1 of 4
LOC105369690	XR_931424.4	n.1156+482T>G		intron_variant	Intron 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ST8SIA1	ENST00000544732.5	n.298-6420T>G		intron_variant	Intron 4 of 5	5

Frequencies

GnomAD3 genomes AF: 0.544 AC: 82626 AN: 152024 Hom.: 23689 Cov.: 32

Gnomad AFR AF: 0.451

Gnomad AMI AF: 0.769

Gnomad AMR AF: 0.499

Gnomad ASJ AF: 0.543

Gnomad EAS AF: 0.124

Gnomad SAS AF: 0.351

Gnomad FIN AF: 0.640

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.638

Gnomad OTH AF: 0.540

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

GnomAD4 genome AF: 0.543 AC: 82670 AN: 152140 Hom.: 23699 Cov.: 32 AF XY: 0.535 AC XY: 39771 AN XY: 74364

African (AFR) AF: 0.450 AC: 18688 AN: 41488

American (AMR) AF: 0.499 AC: 7627 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.543 AC: 1884 AN: 3470

East Asian (EAS) AF: 0.124 AC: 644 AN: 5176

South Asian (SAS) AF: 0.352 AC: 1696 AN: 4820

European-Finnish (FIN) AF: 0.640 AC: 6772 AN: 10576

Middle Eastern (MID) AF: 0.517 AC: 152 AN: 294

European-Non Finnish (NFE) AF: 0.638 AC: 43372 AN: 68002

Other (OTH) AF: 0.538 AC: 1134 AN: 2108

Alfa AF: 0.460 Hom.: 1634

Bravo AF: 0.533

Asia WGS AF: 0.254 AC: 884 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	1.5
DANN	Benign	0.90
PhyloP100		0.32

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs759582; hg19: chr12-22229979;