rs2978023

Variant names:

• chr8-133536328-T-C
• rs2978023
• NM_173344.3:c.-429+9446A>G

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+9446A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.29 in 152,112 control chromosomes in the GnomAD database, including 7,571 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 0.29 (7571 hom., cov: 32)
• Consequence: ST3GAL1 NM_173344.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.40
• Publications: 3 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=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.384 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173344.3. 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
	ST3GAL1	NM_173344.3	MANE Select	c.-429+9446A>G		intron	N/A	NP_775479.1	Q11201
	ST3GAL1	NM_003033.4		c.-632+9446A>G		intron	N/A	NP_003024.1	Q11201

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ST3GAL1	ENST00000522652.6	TSL:1 MANE Select	c.-429+9446A>G		intron	N/A	ENSP00000430515.1	Q11201
	ST3GAL1	ENST00000521180.5	TSL:1	c.-632+9446A>G		intron	N/A	ENSP00000428540.1	Q11201
	ST3GAL1	ENST00000518298.5	TSL:1	n.349+9446A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.291 AC: 44162 AN: 151994 Hom.: 7568 Cov.: 32

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.464

Gnomad AMR AF: 0.267

Gnomad ASJ AF: 0.373

Gnomad EAS AF: 0.0528

Gnomad SAS AF: 0.264

Gnomad FIN AF: 0.396

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.388

Gnomad OTH AF: 0.314

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

GnomAD4 genome AF: 0.290 AC: 44174 AN: 152112 Hom.: 7571 Cov.: 32 AF XY: 0.288 AC XY: 21404 AN XY: 74342

African (AFR) AF: 0.132 AC: 5493 AN: 41528

American (AMR) AF: 0.267 AC: 4068 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.373 AC: 1296 AN: 3472

East Asian (EAS) AF: 0.0529 AC: 274 AN: 5182

South Asian (SAS) AF: 0.264 AC: 1274 AN: 4818

European-Finnish (FIN) AF: 0.396 AC: 4182 AN: 10560

Middle Eastern (MID) AF: 0.408 AC: 120 AN: 294

European-Non Finnish (NFE) AF: 0.388 AC: 26387 AN: 67986

Other (OTH) AF: 0.312 AC: 658 AN: 2108

Alfa AF: 0.347 Hom.: 9393

Bravo AF: 0.275

Asia WGS AF: 0.150 AC: 524 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.073
DANN	Benign	0.53
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: rs2978023; hg19: chr8-134548571;