1-43736342-C-T

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 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

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.74

Publications

0 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

ST3GAL3 links:

ENSG00000284989 (HGNC:):

ENSG00000284989 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 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
ST3GAL3	NM_006279.5 link	c.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	UniProt
ST3GAL3	ENST00000347631.8 link	c.80C>T	p.Ala27Val	missense_variant	Exon 2 of 12	5	NM_006279.5	ENSP00000317192.6	Q11203-1
ENSG00000284989	ENST00000645057.1 link	n.*1402C>T		non_coding_transcript_exon_variant	Exon 16 of 26			ENSP00000494063.1	A0A2R8Y4U1
ENSG00000284989	ENST00000645057.1 link	n.*1402C>T		3_prime_UTR_variant	Exon 16 of 26			ENSP00000494063.1	A0A2R8Y4U1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251480

AF XY:

0.00000736

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461870

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727238

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000360

AC:

AN:

1111998

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

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

Developmental and epileptic encephalopathy

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

BayesDel_noAF

Benign

-0.16

CADD

Uncertain

(source)

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

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

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

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;.;.

PhyloP100

3.7

PrimateAI

Uncertain

0.70

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

GERP RS

5.0

PromoterAI

-0.037

Neutral

(source)

Varity_R

0.23

gMVP

0.82

Mutation Taster

=71/29

polymorphism

(source)

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

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1-43736342-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over