NM_006279.5:c.401A>G

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_006279.5(ST3GAL3):c.401A>G(p.Asn134Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000118 in 1,613,804 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 Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N134Y) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

ST3GAL3
NM_006279.5 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:4B:1

Conservation

PhyloP100: 5.27

Publications

2 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 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ST3GAL3	NM_006279.5 link	c.401A>G	p.Asn134Ser	missense_variant	Exon 7 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.401A>G	p.Asn134Ser	missense_variant	Exon 7 of 12	5	NM_006279.5	ENSP00000317192.6	Q11203-1
ENSG00000284989	ENST00000645057.1 link	n.*1723A>G		non_coding_transcript_exon_variant	Exon 21 of 26			ENSP00000494063.1	A0A2R8Y4U1
ENSG00000284989	ENST00000645057.1 link	n.*1723A>G		3_prime_UTR_variant	Exon 21 of 26			ENSP00000494063.1	A0A2R8Y4U1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152194

Hom.:

Cov.:

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:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251252

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000123

AC:

AN:

1461610

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

727110

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000756

AC:

AN:

39700

South Asian (SAS)

AF:

0.000162

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53166

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111994

Other (OTH)

AF:

0.00

AC:

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.00000657

AC:

AN:

152194

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41440

American (AMR)

AF:

0.00

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000192

AC:

AN:

5198

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68024

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:4Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 02, 2016

Genetic Services Laboratory, University of Chicago

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Developmental and epileptic encephalopathy

Uncertain:1

Jun 20, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 436873). This variant has not been reported in the literature in individuals affected with ST3GAL3-related conditions. This variant is present in population databases (rs745451424, gnomAD 0.003%). This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 134 of the ST3GAL3 protein (p.Asn134Ser). -

Epilepsy due to perinatal stroke

Uncertain:1

Jun 01, 2017

Clinical Molecular Genetics Laboratory, Johns Hopkins All Children's Hospital

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Uncertain:1

Nov 25, 2019

Revvity Omics, Revvity

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Intellectual disability, autosomal recessive 12;C3554316:Developmental and epileptic encephalopathy, 15

Benign:1

Sep 20, 2024

3billion

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The homozygous variant was found in patients diagnosed with another variant in a different gene, with no symptoms related to the gene containing the homozygous variant. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.62

CADD

Uncertain

(source)

DANN

Benign

0.86

DEOGEN2

Benign

0.090

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

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.30

FATHMM_MKL

Uncertain

0.85

LIST_S2

Uncertain

0.88

.;D;D;D;D;D;D;D;D;D;D;D;.;D;D;T;D;D;D;D;D;D;D;D;D;.;D;D

M_CAP

Benign

0.0070

MetaRNN

Benign

0.098

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

Benign

-1.1

MutationAssessor

Benign

0.28

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

PhyloP100

5.3

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-1.0

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

REVEL

Benign

0.12

Sift

Benign

0.46

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

Sift4G

Benign

0.48

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

Polyphen

0.18

B;P;B;B;B;.;.;.;.;P;P;P;B;.;P;.;.;B;.;.;B;P;.;P;P;B;.;.

Vest4

0.44, 0.47, 0.43, 0.46, 0.39, 0.44, 0.47, 0.45, 0.47, 0.39, 0.48, 0.44

MutPred

0.36

Loss of helix (P = 0.079);.;.;.;.;Loss of helix (P = 0.079);.;.;.;Loss of helix (P = 0.079);.;.;Loss of helix (P = 0.079);Loss of helix (P = 0.079);.;.;Loss of helix (P = 0.079);Loss of helix (P = 0.079);.;.;Loss of helix (P = 0.079);.;Loss of helix (P = 0.079);.;.;.;.;.;

MVP

0.093

MPC

0.74

ClinPred

0.15

GERP RS

3.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.040

gMVP

0.39

Mutation Taster

=78/22

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.49

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.49

Position offset: 1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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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