chr11-124637059-T-C

Variant names:

• chr11-124637059-T-C
• rs781746246
• NM_170601.5:c.1464A>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 4P and 2B. PM2 PP3_Moderate BP6_Moderate

The NM_170601.5(SIAE):​c.1464A>G​(p.Glu488Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SIAE NM_170601.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0510
• 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: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
• BP6: Variant 11-124637059-T-C is Benign according to our data. Variant chr11-124637059-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2087423.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIAE	NM_170601.5	c.1464A>G	p.Glu488Glu	synonymous_variant	Exon 10 of 10	ENST00000263593.8	NP_733746.1
SIAE	NM_001199922.2	c.1359A>G	p.Glu453Glu	synonymous_variant	Exon 12 of 12		NP_001186851.1
SIAE	XM_047427132.1	c.891A>G	p.Glu297Glu	synonymous_variant	Exon 7 of 7		XP_047283088.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIAE	ENST00000263593.8	c.1464A>G	p.Glu488Glu	synonymous_variant	Exon 10 of 10	1	NM_170601.5	ENSP00000263593.3
SIAE	ENST00000618733.4	c.1359A>G	p.Glu453Glu	synonymous_variant	Exon 12 of 12	1		ENSP00000478211.1
SIAE	ENST00000545756.5	c.1359A>G	p.Glu453Glu	synonymous_variant	Exon 11 of 11	5		ENSP00000437877.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jan 18, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	21
DANN	Benign	0.67
PhyloP100		-0.051

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.87		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.87		Position offset: 5

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

Other links and lift over

dbSNP: rs781746246; hg19: chr11-124506955;