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GeneBe

11-124637071-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_170601.5(SIAE):c.1452G>A(p.Thr484=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.046 in 1,613,918 control chromosomes in the GnomAD database, including 7,215 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 3325 hom., cov: 32)
Exomes 𝑓: 0.037 ( 3890 hom. )

Consequence

SIAE
NM_170601.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.82
Variant links:
Genes affected
SIAE (HGNC:18187): (sialic acid acetylesterase) This gene encodes an enzyme which removes 9-O-acetylation modifications from sialic acids. Mutations in this gene are associated with susceptibility to autoimmune disease 6. Multiple transcript variants encoding different isoforms, found either in the cytosol or in the lysosome, have been found for this gene.[provided by RefSeq, Feb 2011]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 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=-0.7).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 11-124637071-C-T is Benign according to our data. Variant chr11-124637071-C-T is described in ClinVar as [Benign]. Clinvar id is 1168498.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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=-1.82 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.386 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SIAENM_170601.5 linkuse as main transcriptc.1452G>A p.Thr484= synonymous_variant 10/10 ENST00000263593.8
SIAENM_001199922.2 linkuse as main transcriptc.1347G>A p.Thr449= synonymous_variant 12/12
SIAEXM_047427132.1 linkuse as main transcriptc.879G>A p.Thr293= synonymous_variant 7/7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SIAEENST00000263593.8 linkuse as main transcriptc.1452G>A p.Thr484= synonymous_variant 10/101 NM_170601.5 P2Q9HAT2-1
SIAEENST00000618733.4 linkuse as main transcriptc.1347G>A p.Thr449= synonymous_variant 12/121 A2Q9HAT2-2
SIAEENST00000545756.5 linkuse as main transcriptc.1347G>A p.Thr449= synonymous_variant 11/115 A2Q9HAT2-2

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.130
AC:
19775
AN:
151908
Hom.:
3300
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.391
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0669
Gnomad ASJ
AF:
0.0369
Gnomad EAS
AF:
0.101
Gnomad SAS
AF:
0.0381
Gnomad FIN
AF:
0.00576
Gnomad MID
AF:
0.0475
Gnomad NFE
AF:
0.0223
Gnomad OTH
AF:
0.102
GnomAD3 exomes
AF:
0.0545
AC:
13706
AN:
251460
Hom.:
1542
AF XY:
0.0472
AC XY:
6420
AN XY:
135902
show subpopulations
Gnomad AFR exome
AF:
0.405
Gnomad AMR exome
AF:
0.0338
Gnomad ASJ exome
AF:
0.0390
Gnomad EAS exome
AF:
0.102
Gnomad SAS exome
AF:
0.0318
Gnomad FIN exome
AF:
0.00513
Gnomad NFE exome
AF:
0.0207
Gnomad OTH exome
AF:
0.0391
GnomAD4 exome
AF:
0.0372
AC:
54455
AN:
1461890
Hom.:
3890
Cov.:
31
AF XY:
0.0361
AC XY:
26250
AN XY:
727246
show subpopulations
Gnomad4 AFR exome
AF:
0.409
Gnomad4 AMR exome
AF:
0.0381
Gnomad4 ASJ exome
AF:
0.0403
Gnomad4 EAS exome
AF:
0.137
Gnomad4 SAS exome
AF:
0.0348
Gnomad4 FIN exome
AF:
0.00648
Gnomad4 NFE exome
AF:
0.0229
Gnomad4 OTH exome
AF:
0.0593
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.131
AC:
19850
AN:
152028
Hom.:
3325
Cov.:
32
AF XY:
0.126
AC XY:
9371
AN XY:
74326
show subpopulations
Gnomad4 AFR
AF:
0.391
Gnomad4 AMR
AF:
0.0667
Gnomad4 ASJ
AF:
0.0369
Gnomad4 EAS
AF:
0.101
Gnomad4 SAS
AF:
0.0378
Gnomad4 FIN
AF:
0.00576
Gnomad4 NFE
AF:
0.0223
Gnomad4 OTH
AF:
0.100
Alfa
AF:
0.0474
Hom.:
1045
Bravo
AF:
0.148
Asia WGS
AF:
0.121
AC:
421
AN:
3478
EpiCase
AF:
0.0234
EpiControl
AF:
0.0225

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

SIAE-related disorder Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesNov 14, 2019This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJan 31, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.70
Cadd
Benign
0.12
Dann
Benign
0.81

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs7941327; hg19: chr11-124506967; COSMIC: COSV52514648; COSMIC: COSV52514648; API