11-124637048-CACTGCTTATAT-C

Variant names:

• chr11-124637048-CACTGCTTATAT-C
• NM_170601.5:c.1464_1474delATATAAGCAGT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

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. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.10
• Publications: 0 publications found

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]

SIAE Gene-Disease associations (from GenCC):

• autoimmune disease, susceptibility to, 6

  Inheritance: Unknown Classification: LIMITED Submitted by: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_170601.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIAE	NM_170601.5	MANE Select	c.1464_1474delATATAAGCAGT	p.Tyr489SerfsTer7	frameshift	Exon 10 of 10	NP_733746.1	Q9HAT2-1
	SIAE	NM_001199922.2		c.1359_1369delATATAAGCAGT	p.Tyr454SerfsTer7	frameshift	Exon 12 of 12	NP_001186851.1	Q9HAT2-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIAE	ENST00000263593.8	TSL:1 MANE Select	c.1464_1474delATATAAGCAGT	p.Tyr489SerfsTer7	frameshift	Exon 10 of 10	ENSP00000263593.3	Q9HAT2-1
	SIAE	ENST00000618733.4	TSL:1	c.1359_1369delATATAAGCAGT	p.Tyr454SerfsTer7	frameshift	Exon 12 of 12	ENSP00000478211.1	Q9HAT2-2
	SIAE	ENST00000899891.1		c.1455_1465delATATAAGCAGT	p.Tyr486SerfsTer7	frameshift	Exon 10 of 10	ENSP00000569950.1

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

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.1

Splicing

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

Other links and lift over

hg19: chr11-124506944;