1-43736390-G-C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_006279.5(ST3GAL3):​c.118+10G>C variant causes a intron 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. 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_006279.5 intron

Scores

16

Clinical Significance

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

Conservation

PhyloP100: 0.618

Publications

5 publications found
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 Gene-Disease associations (from GenCC):
  • developmental and epileptic encephalopathy, 15
    Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
  • intellectual disability, autosomal recessive 12
    Inheritance: AR Classification: STRONG Submitted by: G2P
  • complex neurodevelopmental disorder
    Inheritance: AR Classification: MODERATE Submitted by: ClinGen
  • infantile spasms
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • autosomal recessive non-syndromic intellectual disability
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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: {Uncertain_significance=2, Likely_benign=3}.
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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
BS2
High Homozygotes in GnomAdExome4 at 5 AR,AD gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ST3GAL3NM_006279.5 linkc.118+10G>C intron_variant Intron 2 of 11 ENST00000347631.8 NP_006270.1 Q11203-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ST3GAL3ENST00000347631.8 linkc.118+10G>C intron_variant Intron 2 of 11 5 NM_006279.5 ENSP00000317192.6 Q11203-1
ENSG00000284989ENST00000645057.1 linkn.*1440+10G>C intron_variant Intron 16 of 25 ENSP00000494063.1 A0A2R8Y4U1

Frequencies

GnomAD3 genomes
AF:
0.00101
AC:
154
AN:
152160
Hom.:
0
Cov.:
32
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
GnomAD2 exomes
AF:
0.000923
AC:
232
AN:
251486
AF XY:
0.000949
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 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.:
5
Cov.:
31
AF XY:
0.00163
AC XY:
1184
AN XY:
727232
show subpopulations
African (AFR)
AF:
0.000358
AC:
12
AN:
33478
American (AMR)
AF:
0.000425
AC:
19
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26134
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39696
South Asian (SAS)
AF:
0.000348
AC:
30
AN:
86258
European-Finnish (FIN)
AF:
0.000655
AC:
35
AN:
53416
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
0.00203
AC:
2255
AN:
1111998
Other (OTH)
AF:
0.00131
AC:
79
AN:
60396
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.471
Heterozygous variant carriers
0
128
256
385
513
641
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
86
172
258
344
430
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.00101
AC:
154
AN:
152278
Hom.:
0
Cov.:
32
AF XY:
0.00102
AC XY:
76
AN XY:
74472
show subpopulations
African (AFR)
AF:
0.000361
AC:
15
AN:
41562
American (AMR)
AF:
0.000785
AC:
12
AN:
15290
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3470
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5182
South Asian (SAS)
AF:
0.000830
AC:
4
AN:
4822
European-Finnish (FIN)
AF:
0.000565
AC:
6
AN:
10618
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
0.00168
AC:
114
AN:
68014
Other (OTH)
AF:
0.00142
AC:
3
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.507
Heterozygous variant carriers
0
8
15
23
30
38
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
4
8
12
16
20
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.00154
Hom.:
1
Bravo
AF:
0.000963
TwinsUK
AF:
0.00189
AC:
7
ALSPAC
AF:
0.00285
AC:
11
ESP6500AA
AF:
0.00113
AC:
5
ESP6500EA
AF:
0.00174
AC:
15
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
Apr 01, 2025
CeGaT Center for Human Genetics Tuebingen
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

ST3GAL3: BP4, BS2 -

Jan 31, 2017
Eurofins Ntd Llc (ga)
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

-
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Significance:Likely benign
Review Status:no assertion criteria provided
Collection Method:clinical testing

- -

Oct 31, 2018
Athena Diagnostics
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

-
Genome Diagnostics Laboratory, University Medical Center Utrecht
Significance:Likely benign
Review Status:no assertion criteria provided
Collection Method:clinical testing

- -

not specified Uncertain:1
Jul 03, 2014
Genetic Services Laboratory, University of Chicago
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

ST3GAL3-related disorder Benign:1
Jul 10, 2024
PreventionGenetics, part of Exact Sciences
Significance:Likely benign
Review Status:no assertion criteria provided
Collection Method:clinical testing

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). -

Developmental and epileptic encephalopathy Benign:1
Dec 24, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.51
T
BayesDel_noAF
Benign
-0.51
CADD
Benign
18
DANN
Benign
0.81
Eigen
Benign
-0.75
Eigen_PC
Benign
-0.66
FATHMM_MKL
Benign
0.20
N
LIST_S2
Benign
0.62
T;T;T;T;T;T;.;.;T
M_CAP
Benign
0.019
T
MetaRNN
Benign
0.0052
T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-0.94
T
PhyloP100
0.62
PrimateAI
Benign
0.29
T
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
T
GERP RS
5.0
PromoterAI
0.0014
Neutral
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0
gMVP
0.34
Mutation Taster
=95/5
polymorphism

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

Other links and lift over

dbSNP: rs147330005; hg19: chr1-44202061; API