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GeneBe

rs1942663

chr11-124654731-A-G

Variant summary

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

The NM_170601.5(SIAE):c.468T>C(p.Ser156=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0551 in 1,613,912 control chromosomes in the GnomAD database, including 12,958 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.18 ( 6287 hom., cov: 32)
Exomes 𝑓: 0.043 ( 6671 hom. )

Consequence

SIAE
NM_170601.5 synonymous

Scores

2

Clinical Significance

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

Conservation

PhyloP100: -3.20
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=-0.93).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 11-124654731-A-G is Benign according to our data. Variant chr11-124654731-A-G is described in ClinVar as [Benign]. Clinvar id is 1168499.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=-3.2 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 = 0.536 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SIAENM_170601.5 linkuse as main transcriptc.468T>C p.Ser156= synonymous_variant 4/10 ENST00000263593.8
SIAENM_001199922.2 linkuse as main transcriptc.363T>C p.Ser121= synonymous_variant 6/12
SIAEXM_047427133.1 linkuse as main transcriptc.468T>C p.Ser156= synonymous_variant 4/5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SIAEENST00000263593.8 linkuse as main transcriptc.468T>C p.Ser156= synonymous_variant 4/101 NM_170601.5 P2Q9HAT2-1
SIAEENST00000618733.4 linkuse as main transcriptc.363T>C p.Ser121= synonymous_variant 6/121 A2Q9HAT2-2
SIAEENST00000545756.5 linkuse as main transcriptc.363T>C p.Ser121= synonymous_variant 5/115 A2Q9HAT2-2
SIAEENST00000533613.1 linkuse as main transcriptn.492T>C non_coding_transcript_exon_variant 3/34

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.175
AC:
26539
AN:
151928
Hom.:
6250
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.541
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0874
Gnomad ASJ
AF:
0.0410
Gnomad EAS
AF:
0.102
Gnomad SAS
AF:
0.0392
Gnomad FIN
AF:
0.00979
Gnomad MID
AF:
0.0665
Gnomad NFE
AF:
0.0236
Gnomad OTH
AF:
0.143
GnomAD3 exomes
AF:
0.0667
AC:
16780
AN:
251472
Hom.:
2721
AF XY:
0.0564
AC XY:
7660
AN XY:
135908
show subpopulations
Gnomad AFR exome
AF:
0.555
Gnomad AMR exome
AF:
0.0422
Gnomad ASJ exome
AF:
0.0436
Gnomad EAS exome
AF:
0.103
Gnomad SAS exome
AF:
0.0332
Gnomad FIN exome
AF:
0.00878
Gnomad NFE exome
AF:
0.0218
Gnomad OTH exome
AF:
0.0453
GnomAD4 exome
AF:
0.0427
AC:
62370
AN:
1461866
Hom.:
6671
Cov.:
33
AF XY:
0.0408
AC XY:
29648
AN XY:
727236
show subpopulations
Gnomad4 AFR exome
AF:
0.566
Gnomad4 AMR exome
AF:
0.0478
Gnomad4 ASJ exome
AF:
0.0456
Gnomad4 EAS exome
AF:
0.138
Gnomad4 SAS exome
AF:
0.0361
Gnomad4 FIN exome
AF:
0.00996
Gnomad4 NFE exome
AF:
0.0237
Gnomad4 OTH exome
AF:
0.0714
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.175
AC:
26632
AN:
152046
Hom.:
6287
Cov.:
32
AF XY:
0.170
AC XY:
12622
AN XY:
74334
show subpopulations
Gnomad4 AFR
AF:
0.542
Gnomad4 AMR
AF:
0.0872
Gnomad4 ASJ
AF:
0.0410
Gnomad4 EAS
AF:
0.102
Gnomad4 SAS
AF:
0.0388
Gnomad4 FIN
AF:
0.00979
Gnomad4 NFE
AF:
0.0236
Gnomad4 OTH
AF:
0.141
Alfa
AF:
0.0627
Hom.:
1869
Bravo
AF:
0.199
Asia WGS
AF:
0.136
AC:
473
AN:
3478
EpiCase
AF:
0.0248
EpiControl
AF:
0.0239

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 testingInvitaeFeb 01, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.93
Cadd
Benign
0.087
Dann
Benign
0.43

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
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: rs1942663; hg19: chr11-124524627; COSMIC: COSV55015429; COSMIC: COSV55015429; API