rs147330005

Positions:

chr1-43736390-G-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_001350619.2(ST3GAL3):c.128G>C(p.Ser43Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0016 in 1,614,146 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0010 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0017 ( 5 hom. )

Consequence

ST3GAL3
NM_001350619.2 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:6

Conservation

PhyloP100: 0.618

Variant links:

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]

ST3GAL3 links:

ENSG00000284989 (HGNC:):

ENSG00000284989 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005205542).

BP6

Variant 1-43736390-G-C is Benign according to our data. Variant chr1-43736390-G-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 195263.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=3, Uncertain_significance=2}. Variant chr1-43736390-G-C is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00101 (154/152278) while in subpopulation NFE AF= 0.00168 (114/68014). AF 95% confidence interval is 0.00143. There are 0 homozygotes in gnomad4. There are 76 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ST3GAL3	NM_006279.5 linkuse as main transcript	c.118+10G>C		intron_variant		ENST00000347631.8	NP_006270.1	Q11203-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ST3GAL3	ENST00000347631.8 linkuse as main transcript	c.118+10G>C		intron_variant		5	NM_006279.5	ENSP00000317192.6		Q11203-1
ENSG00000284989	ENST00000645057.1 linkuse as main transcript	n.*1440+10G>C		intron_variant				ENSP00000494063.1		A0A2R8Y4U1

Frequencies

GnomAD3 genomes

AF:

0.00101

AC:

154

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000362

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000786

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.000565

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00168

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.000923

AC:

232

AN:

251486

Hom.:

AF XY:

0.000949

AC XY:

129

AN XY:

135920

show subpopulations

Gnomad AFR exome

AF:

0.000492

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000196

Gnomad FIN exome

AF:

0.000554

Gnomad NFE exome

AF:

0.00171

Gnomad OTH exome

AF:

0.000977

GnomAD4 exome

AF:

0.00166

AC:

2430

AN:

1461868

Hom.:

Cov.:

AF XY:

0.00163

AC XY:

1184

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.000358

Gnomad4 AMR exome

AF:

0.000425

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000348

Gnomad4 FIN exome

AF:

0.000655

Gnomad4 NFE exome

AF:

0.00203

Gnomad4 OTH exome

AF:

0.00131

GnomAD4 genome

AF:

0.00101

AC:

154

AN:

152278

Hom.:

Cov.:

AF XY:

0.00102

AC XY:

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.000361

Gnomad4 AMR

AF:

0.000785

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000830

Gnomad4 FIN

AF:

0.000565

Gnomad4 NFE

AF:

0.00168

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00154

Hom.:

Bravo

AF:

0.000963

TwinsUK

AF:

0.00189

AC:

ALSPAC

AF:

0.00285

AC:

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.00174

AC:

ExAC

AF:

0.000997

AC:

121

EpiCase

AF:

0.00153

EpiControl

AF:

0.00160

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:2Benign:6

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:4

Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Oct 31, 2018	- -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Aug 01, 2022	ST3GAL3: BP4, BS2 -
Uncertain significance, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jan 31, 2017	- -

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Jul 03, 2014

- -

ST3GAL3-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 10, 2024

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Early infantile epileptic encephalopathy with suppression bursts

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 17, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Benign

0.81

Eigen

Benign

-0.75

Eigen_PC

Benign

-0.66

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.62

T;T;T;T;T;T;.;.;T

M_CAP

Benign

0.019

MetaRNN

Benign

0.0052

T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.94

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.77

N;.;.;.;N;N;N;N;.

REVEL

Benign

0.16

Sift

Benign

0.68

T;.;.;.;T;T;T;T;.

Sift4G

Benign

0.76

T;T;.;.;T;T;T;T;.

Polyphen

0.0020, 0.017

.;B;.;.;B;B;.;B;.

Vest4

0.29

MVP

0.16

MPC

0.52

ClinPred

0.0075

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

gMVP

0.34

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over