8-133466286-G-A

Variant names:

• chr8-133466286-G-A
• rs6986303
• NM_173344.3:c.307-196C>T

Variant summary

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

The NM_173344.3(ST3GAL1):​c.307-196C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.338 in 152,016 control chromosomes in the GnomAD database, including 9,210 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 0.34 (9210 hom., cov: 32)
• Consequence: ST3GAL1 NM_173344.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.13
• Publications: 12 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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.625 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ST3GAL1	NM_173344.3	c.307-196C>T		intron_variant	Intron 5 of 9	ENST00000522652.6	NP_775479.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ST3GAL1	ENST00000522652.6	c.307-196C>T		intron_variant	Intron 5 of 9	1	NM_173344.3	ENSP00000430515.1

Frequencies

GnomAD3 genomes AF: 0.338 AC: 51380 AN: 151898 Hom.: 9199 Cov.: 32

Gnomad AFR AF: 0.402

Gnomad AMI AF: 0.365

Gnomad AMR AF: 0.354

Gnomad ASJ AF: 0.288

Gnomad EAS AF: 0.644

Gnomad SAS AF: 0.430

Gnomad FIN AF: 0.282

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.278

Gnomad OTH AF: 0.327

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

GnomAD4 genome AF: 0.338 AC: 51434 AN: 152016 Hom.: 9210 Cov.: 32 AF XY: 0.342 AC XY: 25412 AN XY: 74312

African (AFR) AF: 0.402 AC: 16673 AN: 41468

American (AMR) AF: 0.355 AC: 5420 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.288 AC: 998 AN: 3468

East Asian (EAS) AF: 0.644 AC: 3307 AN: 5138

South Asian (SAS) AF: 0.429 AC: 2070 AN: 4822

European-Finnish (FIN) AF: 0.282 AC: 2982 AN: 10570

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.278 AC: 18873 AN: 67956

Other (OTH) AF: 0.335 AC: 707 AN: 2112

Alfa AF: 0.298 Hom.: 31591

Bravo AF: 0.346

Asia WGS AF: 0.530 AC: 1841 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	8.0
DANN	Benign	0.43
PhyloP100		1.1
Mutation Taster		=21/79	disease causing

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: rs6986303; hg19: chr8-134478529;