rs80055718

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006279.5(ST3GAL3):​c.892-9G>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0579 in 1,614,058 control chromosomes in the GnomAD database, including 3,083 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.043 ( 211 hom., cov: 32)
Exomes 𝑓: 0.059 ( 2872 hom. )

Consequence

ST3GAL3
NM_006279.5 splice_polypyrimidine_tract, intron

Scores

2
Splicing: ADA: 0.0001221
2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -1.45
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 Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BP6
Variant 1-43920773-G-A is Benign according to our data. Variant chr1-43920773-G-A is described in ClinVar as [Benign]. Clinvar id is 130375.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0652 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ST3GAL3NM_006279.5 linkuse as main transcriptc.892-9G>A splice_polypyrimidine_tract_variant, intron_variant ENST00000347631.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ST3GAL3ENST00000347631.8 linkuse as main transcriptc.892-9G>A splice_polypyrimidine_tract_variant, intron_variant 5 NM_006279.5 A1Q11203-1

Frequencies

GnomAD3 genomes
AF:
0.0434
AC:
6605
AN:
152090
Hom.:
209
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0125
Gnomad AMI
AF:
0.0450
Gnomad AMR
AF:
0.0310
Gnomad ASJ
AF:
0.0254
Gnomad EAS
AF:
0.000771
Gnomad SAS
AF:
0.0323
Gnomad FIN
AF:
0.0672
Gnomad MID
AF:
0.00633
Gnomad NFE
AF:
0.0668
Gnomad OTH
AF:
0.0320
GnomAD3 exomes
AF:
0.0457
AC:
11465
AN:
251112
Hom.:
345
AF XY:
0.0466
AC XY:
6325
AN XY:
135738
show subpopulations
Gnomad AFR exome
AF:
0.0130
Gnomad AMR exome
AF:
0.0336
Gnomad ASJ exome
AF:
0.0287
Gnomad EAS exome
AF:
0.000272
Gnomad SAS exome
AF:
0.0318
Gnomad FIN exome
AF:
0.0622
Gnomad NFE exome
AF:
0.0632
Gnomad OTH exome
AF:
0.0505
GnomAD4 exome
AF:
0.0595
AC:
86915
AN:
1461850
Hom.:
2872
Cov.:
37
AF XY:
0.0588
AC XY:
42765
AN XY:
727228
show subpopulations
Gnomad4 AFR exome
AF:
0.0102
Gnomad4 AMR exome
AF:
0.0328
Gnomad4 ASJ exome
AF:
0.0283
Gnomad4 EAS exome
AF:
0.000504
Gnomad4 SAS exome
AF:
0.0350
Gnomad4 FIN exome
AF:
0.0626
Gnomad4 NFE exome
AF:
0.0672
Gnomad4 OTH exome
AF:
0.0529
GnomAD4 genome
AF:
0.0435
AC:
6614
AN:
152208
Hom.:
211
Cov.:
32
AF XY:
0.0423
AC XY:
3150
AN XY:
74402
show subpopulations
Gnomad4 AFR
AF:
0.0125
Gnomad4 AMR
AF:
0.0313
Gnomad4 ASJ
AF:
0.0254
Gnomad4 EAS
AF:
0.000773
Gnomad4 SAS
AF:
0.0329
Gnomad4 FIN
AF:
0.0672
Gnomad4 NFE
AF:
0.0668
Gnomad4 OTH
AF:
0.0317
Alfa
AF:
0.0562
Hom.:
116
Bravo
AF:
0.0388
Asia WGS
AF:
0.0160
AC:
55
AN:
3478
EpiCase
AF:
0.0574
EpiControl
AF:
0.0573

ClinVar

Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:3
Likely benign, no assertion criteria providedclinical testingGenetic Services Laboratory, University of Chicago-Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -
Benign, criteria provided, single submitterclinical testingAthena DiagnosticsJun 14, 2017- -
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -
Early infantile epileptic encephalopathy with suppression bursts Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeFeb 01, 2024- -
not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxSep 04, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.88
CADD
Benign
0.13
DANN
Benign
0.69
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.00012
dbscSNV1_RF
Benign
0.0
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.

Other links and lift over

dbSNP: rs80055718; hg19: chr1-44386445; COSMIC: COSV53512497; COSMIC: COSV53512497; API