Menu
GeneBe

11-126408308-T-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_001254757.2(ST3GAL4):c.439T>C(p.Leu147=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0787 in 1,613,794 control chromosomes in the GnomAD database, including 5,939 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.073 ( 577 hom., cov: 32)
Exomes 𝑓: 0.079 ( 5362 hom. )

Consequence

ST3GAL4
NM_001254757.2 splice_region, synonymous

Scores

2
Splicing: ADA: 0.0002615
2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.657
Variant links:
Genes affected
ST3GAL4 (HGNC:10864): (ST3 beta-galactoside alpha-2,3-sialyltransferase 4) This gene encodes a member of the glycosyltransferase 29 family, a group of enzymes involved in protein glycosylation. The encoded protein is targeted to Golgi membranes but may be proteolytically processed and secreted. The gene product may also be involved in the increased expression of sialyl Lewis X antigen seen in inflammatory responses. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.65).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 11-126408308-T-C is Benign according to our data. Variant chr11-126408308-T-C is described in ClinVar as [Benign]. Clinvar id is 257675.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.657 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.195 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ST3GAL4NM_001254757.2 linkuse as main transcriptc.439T>C p.Leu147= splice_region_variant, synonymous_variant 8/11 ENST00000444328.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ST3GAL4ENST00000444328.7 linkuse as main transcriptc.439T>C p.Leu147= splice_region_variant, synonymous_variant 8/115 NM_001254757.2 P4Q11206-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0726
AC:
11040
AN:
152042
Hom.:
575
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0224
Gnomad AMI
AF:
0.0570
Gnomad AMR
AF:
0.112
Gnomad ASJ
AF:
0.0392
Gnomad EAS
AF:
0.205
Gnomad SAS
AF:
0.0608
Gnomad FIN
AF:
0.111
Gnomad MID
AF:
0.0285
Gnomad NFE
AF:
0.0810
Gnomad OTH
AF:
0.0761
GnomAD3 exomes
AF:
0.0865
AC:
21748
AN:
251306
Hom.:
1170
AF XY:
0.0841
AC XY:
11419
AN XY:
135830
show subpopulations
Gnomad AFR exome
AF:
0.0200
Gnomad AMR exome
AF:
0.0993
Gnomad ASJ exome
AF:
0.0425
Gnomad EAS exome
AF:
0.211
Gnomad SAS exome
AF:
0.0571
Gnomad FIN exome
AF:
0.105
Gnomad NFE exome
AF:
0.0805
Gnomad OTH exome
AF:
0.0814
GnomAD4 exome
AF:
0.0793
AC:
115884
AN:
1461634
Hom.:
5362
Cov.:
34
AF XY:
0.0785
AC XY:
57092
AN XY:
727070
show subpopulations
Gnomad4 AFR exome
AF:
0.0183
Gnomad4 AMR exome
AF:
0.0970
Gnomad4 ASJ exome
AF:
0.0432
Gnomad4 EAS exome
AF:
0.220
Gnomad4 SAS exome
AF:
0.0575
Gnomad4 FIN exome
AF:
0.104
Gnomad4 NFE exome
AF:
0.0772
Gnomad4 OTH exome
AF:
0.0734
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0726
AC:
11043
AN:
152160
Hom.:
577
Cov.:
32
AF XY:
0.0773
AC XY:
5748
AN XY:
74400
show subpopulations
Gnomad4 AFR
AF:
0.0223
Gnomad4 AMR
AF:
0.113
Gnomad4 ASJ
AF:
0.0392
Gnomad4 EAS
AF:
0.205
Gnomad4 SAS
AF:
0.0610
Gnomad4 FIN
AF:
0.111
Gnomad4 NFE
AF:
0.0810
Gnomad4 OTH
AF:
0.0767
Alfa
AF:
0.0770
Hom.:
1279
Bravo
AF:
0.0698
Asia WGS
AF:
0.122
AC:
422
AN:
3478
EpiCase
AF:
0.0736
EpiControl
AF:
0.0734

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.65
Cadd
Benign
0.53
Dann
Benign
0.49

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.00026
dbscSNV1_RF
Benign
0.040
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: rs2298475; hg19: chr11-126278203; COSMIC: COSV57106578; COSMIC: COSV57106578; API