rs80055718

Positions:

• chr1-43920773-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006279.5(ST3GAL3):​c.892-9G>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0579 in 1,614,058 control chromosomes in the GnomAD database, including 3,083 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.043 (211 hom., cov: 32)
  • Exomes 𝑓: 0.059 (2872 hom.)
• Consequence: ST3GAL3 NM_006279.5 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.0001221
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -1.45

Genes affected

ST3GAL3 (HGNC:10866): (ST3 beta-galactoside alpha-2,3-sialyltransferase 3) 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 apparatus but can be proteolytically processed to a soluble form. This protein is a member of glycosyltransferase family 29. Mutations in this gene have been associated with a form of autosomal recessive nonsymdromic cognitive disability as well as infantile epileptic encephalopathy. Multiple transcript variants encoding several different isoforms have been found for this gene. [provided by RefSeq, Jul 2017]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 1-43920773-G-A is Benign according to our data. Variant chr1-43920773-G-A is described in ClinVar as [Benign]. Clinvar id is 130375.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0652 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ST3GAL3	NM_006279.5	c.892-9G>A		splice_polypyrimidine_tract_variant, intron_variant		ENST00000347631.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ST3GAL3	ENST00000347631.8	c.892-9G>A		splice_polypyrimidine_tract_variant, intron_variant		5	NM_006279.5	A1

Frequencies

GnomAD3 genomes AF: 0.0434 AC: 6605 AN: 152090 Hom.: 209 Cov.: 32

Gnomad AFR AF: 0.0125

Gnomad AMI AF: 0.0450

Gnomad AMR AF: 0.0310

Gnomad ASJ AF: 0.0254

Gnomad EAS AF: 0.000771

Gnomad SAS AF: 0.0323

Gnomad FIN AF: 0.0672

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0668

Gnomad OTH AF: 0.0320

GnomAD3 exomes AF: 0.0457 AC: 11465 AN: 251112 Hom.: 345 AF XY: 0.0466 AC XY: 6325 AN XY: 135738

Gnomad AFR exome AF: 0.0130

Gnomad AMR exome AF: 0.0336

Gnomad ASJ exome AF: 0.0287

Gnomad EAS exome AF: 0.000272

Gnomad SAS exome AF: 0.0318

Gnomad FIN exome AF: 0.0622

Gnomad NFE exome AF: 0.0632

Gnomad OTH exome AF: 0.0505

GnomAD4 exome AF: 0.0595 AC: 86915 AN: 1461850 Hom.: 2872 Cov.: 37 AF XY: 0.0588 AC XY: 42765 AN XY: 727228

Gnomad4 AFR exome AF: 0.0102

Gnomad4 AMR exome AF: 0.0328

Gnomad4 ASJ exome AF: 0.0283

Gnomad4 EAS exome AF: 0.000504

Gnomad4 SAS exome AF: 0.0350

Gnomad4 FIN exome AF: 0.0626

Gnomad4 NFE exome AF: 0.0672

Gnomad4 OTH exome AF: 0.0529

GnomAD4 genome AF: 0.0435 AC: 6614 AN: 152208 Hom.: 211 Cov.: 32 AF XY: 0.0423 AC XY: 3150 AN XY: 74402

Gnomad4 AFR AF: 0.0125

Gnomad4 AMR AF: 0.0313

Gnomad4 ASJ AF: 0.0254

Gnomad4 EAS AF: 0.000773

Gnomad4 SAS AF: 0.0329

Gnomad4 FIN AF: 0.0672

Gnomad4 NFE AF: 0.0668

Gnomad4 OTH AF: 0.0317

Alfa AF: 0.0562 Hom.: 116

Bravo AF: 0.0388

Asia WGS AF: 0.0160 AC: 55 AN: 3478

EpiCase AF: 0.0574

EpiControl AF: 0.0573

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jun 14, 2017	- -
Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 04, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Early infantile epileptic encephalopathy with suppression bursts Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.13
DANN	Benign	0.69
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00012
dbscSNV1_RF	Benign	0.0
SpliceAI score (max)		0.010		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: rs80055718; hg19: chr1-44386445; COSMIC: COSV53512497; COSMIC: COSV53512497;