NM_170601.5:c.1446G>A

Variant names:

• chr11-124637077-C-T
• NM_170601.5:c.1446G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_170601.5(SIAE):​c.1446G>A​(p.Trp482*) variant causes a stop gained change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SIAE NM_170601.5 stop_gained
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.04
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.1446G>A	p.Trp482*	stop_gained	Exon 10 of 10	NP_733746.1	Q9HAT2-1
	SIAE	NM_001199922.2		c.1341G>A	p.Trp447*	stop_gained	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.1446G>A	p.Trp482*	stop_gained	Exon 10 of 10	ENSP00000263593.3	Q9HAT2-1
	SIAE	ENST00000618733.4	TSL:1	c.1341G>A	p.Trp447*	stop_gained	Exon 12 of 12	ENSP00000478211.1	Q9HAT2-2
	SIAE	ENST00000899891.1		c.1437G>A	p.Trp479*	stop_gained	Exon 10 of 10	ENSP00000569950.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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
BayesDel_addAF	Pathogenic	0.62	D
BayesDel_noAF	Pathogenic	0.65
CADD	Pathogenic	39
DANN	Uncertain	0.99
Eigen	Pathogenic	0.84
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Pathogenic	0.97	D
PhyloP100		6.0
Vest4		0.23
GERP RS		5.7
Mutation Taster		=15/185	disease causing

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

Other links and lift over

hg19: chr11-124506973;