rs3120803

chr1-43920943-A-Gchr1-43920943-A-T

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.1038+15A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.903 in 1,597,322 control chromosomes in the GnomAD database, including 652,870 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.85 (55837 hom., cov: 30)
  • Exomes 𝑓: 0.91 (597033 hom.)
• Consequence: ST3GAL3 NM_006279.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -1.20

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=-0.94).
• BP6: Variant 1-43920943-A-G is Benign according to our data. Variant chr1-43920943-A-G is described in ClinVar as [Benign]. Clinvar id is 262909.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-43920943-A-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.92 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ST3GAL3	NM_006279.5	c.1038+15A>G		intron_variant		ENST00000347631.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ST3GAL3	ENST00000347631.8	c.1038+15A>G		intron_variant		5	NM_006279.5	A1

Frequencies

GnomAD3 genomes AF: 0.851 AC: 129294 AN: 151874 Hom.: 55812 Cov.: 30

Gnomad AFR AF: 0.699

Gnomad AMI AF: 0.988

Gnomad AMR AF: 0.876

Gnomad ASJ AF: 0.928

Gnomad EAS AF: 0.849

Gnomad SAS AF: 0.872

Gnomad FIN AF: 0.882

Gnomad MID AF: 0.823

Gnomad NFE AF: 0.926

Gnomad OTH AF: 0.874

GnomAD3 exomes AF: 0.881 AC: 197917 AN: 224564 Hom.: 87552 AF XY: 0.886 AC XY: 107012 AN XY: 120790

Gnomad AFR exome AF: 0.695

Gnomad AMR exome AF: 0.848

Gnomad ASJ exome AF: 0.927

Gnomad EAS exome AF: 0.854

Gnomad SAS exome AF: 0.867

Gnomad FIN exome AF: 0.886

Gnomad NFE exome AF: 0.921

Gnomad OTH exome AF: 0.885

GnomAD4 exome AF: 0.908 AC: 1312307 AN: 1445328 Hom.: 597033 Cov.: 48 AF XY: 0.908 AC XY: 651461 AN XY: 717426

Gnomad4 AFR exome AF: 0.691

Gnomad4 AMR exome AF: 0.851

Gnomad4 ASJ exome AF: 0.926

Gnomad4 EAS exome AF: 0.818

Gnomad4 SAS exome AF: 0.868

Gnomad4 FIN exome AF: 0.889

Gnomad4 NFE exome AF: 0.924

Gnomad4 OTH exome AF: 0.895

GnomAD4 genome AF: 0.851 AC: 129369 AN: 151994 Hom.: 55837 Cov.: 30 AF XY: 0.850 AC XY: 63158 AN XY: 74296

Gnomad4 AFR AF: 0.699

Gnomad4 AMR AF: 0.876

Gnomad4 ASJ AF: 0.928

Gnomad4 EAS AF: 0.849

Gnomad4 SAS AF: 0.872

Gnomad4 FIN AF: 0.882

Gnomad4 NFE AF: 0.926

Gnomad4 OTH AF: 0.876

Alfa AF: 0.913 Hom.: 109629

Bravo AF: 0.843

Asia WGS AF: 0.853 AC: 2967 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Intellectual disability, autosomal recessive 12 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Early infantile epileptic encephalopathy with suppression bursts Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Developmental and epileptic encephalopathy, 15 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.13
Dann	Benign	0.57

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: rs3120803; hg19: chr1-44386615;