1-43736342-C-T

Variant summary

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

The NM_006279.5(ST3GAL3):​c.80C>T​(p.Ala27Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,870 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 (★). Synonymous variant affecting the same amino acid position (i.e. A27A) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

ST3GAL3
NM_006279.5 missense

Scores

8
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.74
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=0.4189244).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ST3GAL3NM_006279.5 linkc.80C>T p.Ala27Val missense_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.80C>T p.Ala27Val missense_variant Exon 2 of 12 5 NM_006279.5 ENSP00000317192.6 Q11203-1
ENSG00000284989ENST00000645057.1 linkn.*1402C>T non_coding_transcript_exon_variant Exon 16 of 26 ENSP00000494063.1 A0A2R8Y4U1
ENSG00000284989ENST00000645057.1 linkn.*1402C>T 3_prime_UTR_variant Exon 16 of 26 ENSP00000494063.1 A0A2R8Y4U1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251480
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135916
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:
0.00000879
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000274
AC:
4
AN:
1461870
Hom.:
0
Cov.:
31
AF XY:
0.00000413
AC XY:
3
AN XY:
727238
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000360
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.00000824
AC:
1
EpiCase
AF:
0.000327
EpiControl
AF:
0.0000593

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
Feb 24, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 27 of the ST3GAL3 protein (p.Ala27Val). This variant is present in population databases (rs751825349, gnomAD 0.0009%). This missense change has been observed in individual(s) with autism (PMID: 35982160). ClinVar contains an entry for this variant (Variation ID: 941994). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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
0.23
BayesDel_addAF
Uncertain
0.056
T
BayesDel_noAF
Benign
-0.16
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.094
T;.;.;.;.;.;.;.;.;.;.;.;.;.;.;T;.;.;.;.;.;T;.;.;.;.;.;.;.;.;.;.;.;.;.;.
Eigen
Benign
0.11
Eigen_PC
Uncertain
0.24
FATHMM_MKL
Uncertain
0.90
D
LIST_S2
Benign
0.84
.;T;T;D;T;D;T;D;D;D;D;T;D;D;D;.;D;D;D;D;D;D;D;D;D;T;D;D;D;D;.;D;.;.;D;D
M_CAP
Benign
0.078
D
MetaRNN
Benign
0.28
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
0.21
D
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
Uncertain
0.70
T
PROVEAN
Benign
-0.94
N;N;N;D;D;N;N;.;.;.;N;.;N;.;N;.;.;N;.;N;.;.;N;.;D;D;N;N;N;N;D;N;D;N;.;.
REVEL
Benign
0.11
Sift
Uncertain
0.0030
D;D;T;D;D;T;T;.;.;.;D;.;D;.;D;.;.;D;.;D;.;.;D;.;D;D;D;T;D;T;D;D;D;T;.;.
Sift4G
Uncertain
0.0090
D;D;T;D;D;D;T;.;.;.;T;.;T;.;D;.;.;D;.;D;.;.;D;.;D;D;T;D;D;D;D;T;D;D;.;.
Polyphen
0.015
B;B;B;.;P;B;B;.;.;.;.;.;B;B;D;B;.;D;.;.;.;B;.;.;P;P;B;D;.;B;P;B;.;B;.;.
Vest4
0.57
MutPred
0.40
Gain of methylation at K29 (P = 0.0829);Gain of methylation at K29 (P = 0.0829);Gain of methylation at K29 (P = 0.0829);Gain of methylation at K29 (P = 0.0829);Gain of methylation at K29 (P = 0.0829);Gain of methylation at K29 (P = 0.0829);Gain of methylation at K29 (P = 0.0829);Gain of methylation at K29 (P = 0.0829);Gain of methylation at K29 (P = 0.0829);Gain of methylation at K29 (P = 0.0829);Gain of methylation at K29 (P = 0.0829);Gain of methylation at K29 (P = 0.0829);Gain of methylation at K29 (P = 0.0829);Gain of methylation at K29 (P = 0.0829);Gain of methylation at K29 (P = 0.0829);Gain of methylation at K29 (P = 0.0829);Gain of methylation at K29 (P = 0.0829);Gain of methylation at K29 (P = 0.0829);Gain of methylation at K29 (P = 0.0829);Gain of methylation at K29 (P = 0.0829);Gain of methylation at K29 (P = 0.0829);Gain of methylation at K29 (P = 0.0829);Gain of methylation at K29 (P = 0.0829);Gain of methylation at K29 (P = 0.0829);Gain of methylation at K29 (P = 0.0829);Gain of methylation at K29 (P = 0.0829);Gain of methylation at K29 (P = 0.0829);Gain of methylation at K29 (P = 0.0829);Gain of methylation at K29 (P = 0.0829);Gain of methylation at K29 (P = 0.0829);Gain of methylation at K29 (P = 0.0829);Gain of methylation at K29 (P = 0.0829);Gain of methylation at K29 (P = 0.0829);Gain of methylation at K29 (P = 0.0829);.;.;
MVP
0.39
MPC
1.4
ClinPred
0.98
D
GERP RS
5.0
Varity_R
0.23
gMVP
0.82

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.060
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: rs751825349; hg19: chr1-44202013; API