1-43736378-C-T

Position:

chr1-43736378-C-T

Variant summary

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

The NM_006279.5(ST3GAL3):c.116C>T(p.Ser39Phe) variant causes a missense, splice region 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. 1/1 splice prediction tools predict no significant impact on normal splicing. 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
NM_006279.5 missense, splice_region

Scores

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]

ST3GAL3 links:

ENSG00000284989 (HGNC:):

ENSG00000284989 links:

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/exons	MANE	Protein	UniProt
ST3GAL3	NM_006279.5 link	c.116C>T	p.Ser39Phe	missense_variant, splice_region_variant	2/12	ENST00000347631.8	NP_006270.1	Q11203-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ST3GAL3	ENST00000347631.8 link	c.116C>T	p.Ser39Phe	missense_variant, splice_region_variant	2/12	5	NM_006279.5	ENSP00000317192.6	Q11203-1
ENSG00000284989	ENST00000645057.1 link	n.*1438C>T		splice_region_variant, non_coding_transcript_exon_variant	16/26			ENSP00000494063.1	A0A2R8Y4U1
ENSG00000284989	ENST00000645057.1 link	n.*1438C>T		3_prime_UTR_variant	16/26			ENSP00000494063.1	A0A2R8Y4U1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152130

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:

0.00

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:

AN:

251486

Hom.:

AF XY:

0.0000221

AC XY:

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:

AN:

1461876

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

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:

AN:

152130

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

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:

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

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 12, 2018

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. 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 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"). This variant has not been reported in the literature in individuals with ST3GAL3-related disease. This variant is present in population databases (rs774202202, ExAC 0.003%). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Uncertain

0.084

BayesDel_noAF

Uncertain

-0.050

CADD

Pathogenic

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

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

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

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

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

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over