8-133547090-A-G

Position:

• chr8-133547090-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_173344.3(ST3GAL1):​c.-581-1164T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 151,636 control chromosomes in the GnomAD database, including 4,756 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 0.21 (4756 hom., cov: 31)
• Consequence: ST3GAL1 NM_173344.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.35

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.416 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ST3GAL1	NM_173344.3	c.-581-1164T>C		intron_variant		ENST00000522652.6	NP_775479.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ST3GAL1	ENST00000522652.6	c.-581-1164T>C		intron_variant		1	NM_173344.3	ENSP00000430515	P1

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31341 AN: 151534 Hom.: 4739 Cov.: 31

Gnomad AFR AF: 0.421

Gnomad AMI AF: 0.0493

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.0496

Gnomad EAS AF: 0.231

Gnomad SAS AF: 0.0782

Gnomad FIN AF: 0.190

Gnomad MID AF: 0.0732

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.158

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

GnomAD4 genome AF: 0.207 AC: 31402 AN: 151636 Hom.: 4756 Cov.: 31 AF XY: 0.207 AC XY: 15359 AN XY: 74070

Gnomad4 AFR AF: 0.421

Gnomad4 AMR AF: 0.198

Gnomad4 ASJ AF: 0.0496

Gnomad4 EAS AF: 0.232

Gnomad4 SAS AF: 0.0784

Gnomad4 FIN AF: 0.190

Gnomad4 NFE AF: 0.101

Gnomad4 OTH AF: 0.157

Alfa AF: 0.109 Hom.: 2153

Bravo AF: 0.223

Asia WGS AF: 0.162 AC: 563 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.26
DANN	Benign	0.64

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: rs3758105; hg19: chr8-134559333;