11-124637048-CACTGCTTATAT-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_170601.5(SIAE):​c.1464_1474delATATAAGCAGT​(p.Tyr489SerfsTer7) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. E488E) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Consequence

SIAE
NM_170601.5 frameshift

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.10
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 Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SIAENM_170601.5 linkc.1464_1474delATATAAGCAGT p.Tyr489SerfsTer7 frameshift_variant Exon 10 of 10 ENST00000263593.8 NP_733746.1 Q9HAT2-1
SIAENM_001199922.2 linkc.1359_1369delATATAAGCAGT p.Tyr454SerfsTer7 frameshift_variant Exon 12 of 12 NP_001186851.1 Q9HAT2-2
SIAEXM_047427132.1 linkc.891_901delATATAAGCAGT p.Tyr298SerfsTer7 frameshift_variant Exon 7 of 7 XP_047283088.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SIAEENST00000263593.8 linkc.1464_1474delATATAAGCAGT p.Tyr489SerfsTer7 frameshift_variant Exon 10 of 10 1 NM_170601.5 ENSP00000263593.3 Q9HAT2-1
SIAEENST00000618733.4 linkc.1359_1369delATATAAGCAGT p.Tyr454SerfsTer7 frameshift_variant Exon 12 of 12 1 ENSP00000478211.1 Q9HAT2-2
SIAEENST00000545756.5 linkc.1359_1369delATATAAGCAGT p.Tyr454SerfsTer7 frameshift_variant Exon 11 of 11 5 ENSP00000437877.1 Q9HAT2-2

Frequencies

GnomAD3 genomes
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
Cov.:
32

ClinVar

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

Submissions by phenotype

not provided Uncertain:1
May 19, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This sequence change creates a premature translational stop signal (p.Tyr489Serfs*7) in the SIAE gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 35 amino acid(s) of the SIAE protein. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SIAE-related conditions. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-124506944; API