ENST00000361392.9:c.116C>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The ENST00000361392.9(ST3GAL3):​c.116C>T​(p.Ser39Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000248 in 1,614,006 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

ST3GAL3
ENST00000361392.9 missense

Scores

9
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.29
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.3047185).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ST3GAL3NM_006279.5 linkc.116C>T p.Ser39Phe missense_variant, splice_region_variant Exon 2 of 12 ENST00000347631.8 NP_006270.1 Q11203-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ST3GAL3ENST00000347631.8 linkc.116C>T p.Ser39Phe missense_variant, splice_region_variant Exon 2 of 12 5 NM_006279.5 ENSP00000317192.6 Q11203-1
ENSG00000284989ENST00000645057.1 linkn.*1438C>T splice_region_variant, non_coding_transcript_exon_variant Exon 16 of 26 ENSP00000494063.1 A0A2R8Y4U1
ENSG00000284989ENST00000645057.1 linkn.*1438C>T 3_prime_UTR_variant Exon 16 of 26 ENSP00000494063.1 A0A2R8Y4U1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152130
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000119
AC:
3
AN:
251486
Hom.:
0
AF XY:
0.0000221
AC XY:
3
AN XY:
135920
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000264
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1461876
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
727242
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152130
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74308
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378
ExAC
AF:
0.0000165
AC:
2

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Early infantile epileptic encephalopathy with suppression bursts Uncertain:1
Jul 12, 2018
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This sequence change replaces serine with phenylalanine at codon 39 of the ST3GAL3 protein (p.Ser39Phe). The serine residue is weakly conserved and there is a large physicochemical difference between serine and phenylalanine. This variant is present in population databases (rs774202202, ExAC 0.003%). This variant has not been reported in the literature in individuals with ST3GAL3-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.18
BayesDel_addAF
Uncertain
0.084
D
BayesDel_noAF
Uncertain
-0.050
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Benign
0.12
T;.;.;.;.;.;.;.;.;.;.;.;.;.;.;T;.;.;.;.;.;T;.;.;.;.;.;.;.;.;.;.;.;.;.;.
Eigen
Uncertain
0.55
Eigen_PC
Uncertain
0.63
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Benign
0.81
.;T;T;T;T;T;D;T;D;T;T;T;T;T;D;.;T;T;T;T;T;T;D;T;T;T;T;T;T;T;.;T;.;.;T;T
M_CAP
Benign
0.048
D
MetaRNN
Benign
0.29
T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Uncertain
-0.26
T
MutationAssessor
Benign
1.8
L;L;L;L;L;L;L;.;.;.;L;.;L;L;L;L;.;L;.;.;.;L;.;.;L;L;L;L;L;L;L;L;L;L;.;.
PrimateAI
Benign
0.43
T
PROVEAN
Benign
-1.3
N;N;N;N;D;D;N;.;.;.;N;.;N;.;N;.;.;N;.;N;.;.;N;.;D;D;N;N;N;D;D;D;N;N;.;.
REVEL
Benign
0.25
Sift
Uncertain
0.0030
D;D;D;D;D;D;D;.;.;.;D;.;D;.;D;.;.;D;.;D;.;.;D;.;D;D;D;D;D;D;D;D;D;D;.;.
Sift4G
Uncertain
0.031
D;D;D;D;D;D;D;.;.;.;D;.;D;.;D;.;.;D;.;D;.;.;D;.;D;D;D;D;D;D;D;D;D;D;.;.
Polyphen
0.98
D;P;D;.;D;P;D;.;.;.;.;.;D;D;P;D;.;D;.;.;.;D;.;.;D;D;P;D;.;D;D;D;.;P;.;.
Vest4
0.51
MutPred
0.40
Loss of disorder (P = 0.0018);Loss of disorder (P = 0.0018);Loss of disorder (P = 0.0018);Loss of disorder (P = 0.0018);Loss of disorder (P = 0.0018);Loss of disorder (P = 0.0018);Loss of disorder (P = 0.0018);Loss of disorder (P = 0.0018);Loss of disorder (P = 0.0018);Loss of disorder (P = 0.0018);Loss of disorder (P = 0.0018);Loss of disorder (P = 0.0018);Loss of disorder (P = 0.0018);Loss of disorder (P = 0.0018);Loss of disorder (P = 0.0018);Loss of disorder (P = 0.0018);Loss of disorder (P = 0.0018);Loss of disorder (P = 0.0018);Loss of disorder (P = 0.0018);Loss of disorder (P = 0.0018);Loss of disorder (P = 0.0018);Loss of disorder (P = 0.0018);Loss of disorder (P = 0.0018);Loss of disorder (P = 0.0018);Loss of disorder (P = 0.0018);Loss of disorder (P = 0.0018);Loss of disorder (P = 0.0018);Loss of disorder (P = 0.0018);Loss of disorder (P = 0.0018);Loss of disorder (P = 0.0018);Loss of disorder (P = 0.0018);Loss of disorder (P = 0.0018);Loss of disorder (P = 0.0018);Loss of disorder (P = 0.0018);.;.;
MVP
0.60
MPC
0.95
ClinPred
0.64
D
GERP RS
5.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0
Varity_R
0.14
gMVP
0.51

Splicing

Name
Calibrated prediction
Score
Prediction
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

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

Other links and lift over

dbSNP: rs774202202; hg19: chr1-44202049; API