rs2978012

Variant names:

• chr8-133526953-C-T
• rs2978012
• NM_173344.3:c.-429+18821G>A

Variant summary

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

The NM_173344.3(ST3GAL1):​c.-429+18821G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 151,924 control chromosomes in the GnomAD database, including 6,971 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 0.28 (6971 hom., cov: 31)
• Consequence: ST3GAL1 NM_173344.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.334
• Publications: 2 publications found

Genes affected

ST3GAL1 (HGNC:10862): (ST3 beta-galactoside alpha-2,3-sialyltransferase 1) The protein encoded by this gene is a type II membrane protein that catalyzes the transfer of sialic acid from CMP-sialic acid to galactose-containing substrates. The encoded protein is normally found in the Golgi but can be proteolytically processed to a soluble form. Correct glycosylation of the encoded protein may be critical to its sialyltransferase activity. This protein, which is a member of glycosyltransferase family 29, can use the same acceptor substrates as does sialyltransferase 4B. Two transcript variants encoding the same protein have been found for this gene. Other transcript variants may exist, but have not been fully characterized yet. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.362 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ST3GAL1	NM_173344.3	c.-429+18821G>A		intron_variant	Intron 2 of 9	ENST00000522652.6	NP_775479.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ST3GAL1	ENST00000522652.6	c.-429+18821G>A		intron_variant	Intron 2 of 9	1	NM_173344.3	ENSP00000430515.1

Frequencies

GnomAD3 genomes AF: 0.283 AC: 42962 AN: 151806 Hom.: 6968 Cov.: 31

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.430

Gnomad AMR AF: 0.258

Gnomad ASJ AF: 0.355

Gnomad EAS AF: 0.0534

Gnomad SAS AF: 0.264

Gnomad FIN AF: 0.364

Gnomad MID AF: 0.363

Gnomad NFE AF: 0.366

Gnomad OTH AF: 0.299

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

GnomAD4 genome AF: 0.283 AC: 42954 AN: 151924 Hom.: 6971 Cov.: 31 AF XY: 0.280 AC XY: 20797 AN XY: 74252

African (AFR) AF: 0.155 AC: 6439 AN: 41422

American (AMR) AF: 0.258 AC: 3934 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.355 AC: 1232 AN: 3470

East Asian (EAS) AF: 0.0535 AC: 277 AN: 5176

South Asian (SAS) AF: 0.264 AC: 1270 AN: 4810

European-Finnish (FIN) AF: 0.364 AC: 3830 AN: 10534

Middle Eastern (MID) AF: 0.366 AC: 107 AN: 292

European-Non Finnish (NFE) AF: 0.366 AC: 24850 AN: 67932

Other (OTH) AF: 0.296 AC: 625 AN: 2108

Alfa AF: 0.336 Hom.: 35108

Bravo AF: 0.269

Asia WGS AF: 0.148 AC: 517 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	13
DANN	Benign	0.80
PhyloP100		0.33
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: rs2978012; hg19: chr8-134539196;