chr11-124637008-G-GGGA

Variant names:

• chr11-124637008-G-GGGA
• rs1248299282
• NM_170601.5:c.1512_1514dupTCC

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PM4_Supporting

The NM_170601.5(SIAE):​c.1512_1514dupTCC​(p.Pro505dup) variant causes a disruptive inframe insertion change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SIAE NM_170601.5 disruptive_inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.58
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_170601.5. Strenght limited to Supporting due to length of the change: 1aa.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIAE	NM_170601.5	c.1512_1514dupTCC	p.Pro505dup	disruptive_inframe_insertion	Exon 10 of 10	ENST00000263593.8	NP_733746.1
SIAE	NM_001199922.2	c.1407_1409dupTCC	p.Pro470dup	disruptive_inframe_insertion	Exon 12 of 12		NP_001186851.1
SIAE	XM_047427132.1	c.939_941dupTCC	p.Pro314dup	disruptive_inframe_insertion	Exon 7 of 7		XP_047283088.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIAE	ENST00000263593.8	c.1512_1514dupTCC	p.Pro505dup	disruptive_inframe_insertion	Exon 10 of 10	1	NM_170601.5	ENSP00000263593.3
SIAE	ENST00000618733.4	c.1407_1409dupTCC	p.Pro470dup	disruptive_inframe_insertion	Exon 12 of 12	1		ENSP00000478211.1
SIAE	ENST00000545756.5	c.1407_1409dupTCC	p.Pro470dup	disruptive_inframe_insertion	Exon 11 of 11	5		ENSP00000437877.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.6

Splicing

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

Other links and lift over

dbSNP: rs1248299282; hg19: chr11-124506904;