rs144510878

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_170601.5(SIAE):c.935C>T(p.Thr312Met) variant causes a missense change. The variant allele was found at a frequency of 0.00118 in 1,614,190 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. T312T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0010 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 1 hom. )

Consequence

SIAE
NM_170601.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1O:1

Conservation

PhyloP100: 6.17

Publications

10 publications found

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]

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

SIAE links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIAE	NM_170601.5	MANE Select	c.935C>T	p.Thr312Met	missense	Exon 7 of 10	NP_733746.1
	SIAE	NM_001199922.2		c.830C>T	p.Thr277Met	missense	Exon 9 of 12	NP_001186851.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SIAE	ENST00000263593.8	TSL:1 MANE Select	c.935C>T	p.Thr312Met	missense	Exon 7 of 10	ENSP00000263593.3
SIAE	ENST00000618733.4	TSL:1	c.830C>T	p.Thr277Met	missense	Exon 9 of 12	ENSP00000478211.1
SIAE	ENST00000545756.5	TSL:5	c.830C>T	p.Thr277Met	missense	Exon 8 of 11	ENSP00000437877.1

Frequencies

GnomAD3 genomes

AF:

0.00102

AC:

155

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00104

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00185

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.00101

AC:

254

AN:

251420

AF XY:

0.00108

show subpopulations

Gnomad AFR exome

AF:

0.000431

Gnomad AMR exome

AF:

0.000289

Gnomad ASJ exome

AF:

0.00119

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000831

Gnomad NFE exome

AF:

0.00175

Gnomad OTH exome

AF:

0.00130

GnomAD4 exome

AF:

0.00120

AC:

1748

AN:

1461882

Hom.:

Cov.:

AF XY:

0.00115

AC XY:

834

AN XY:

727242

show subpopulations

African (AFR)

AF:

0.000329

AC:

AN:

33480

American (AMR)

AF:

0.000246

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00149

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000756

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00107

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00140

AC:

1556

AN:

1112002

Other (OTH)

AF:

0.00116

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

196

294

392

490

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

150

200

250

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00102

AC:

156

AN:

152308

Hom.:

Cov.:

AF XY:

0.000873

AC XY:

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.000241

AC:

AN:

41564

American (AMR)

AF:

0.000131

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00144

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00104

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00187

AC:

127

AN:

68024

Other (OTH)

AF:

0.000473

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00145

Hom.:

Bravo

AF:

0.000824

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00209

AC:

ExAC

AF:

0.00121

AC:

147

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00164

EpiControl

AF:

0.00154

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1Other:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 312 of the SIAE protein (p.Thr312Met). This variant is present in population databases (rs144510878, gnomAD 0.2%), and has an allele count higher than expected for a pathogenic variant. This missense change has been observed in individual(s) with autoimmune disorders (PMID: 20555325, 22257840, 23011869). ClinVar contains an entry for this variant (Variation ID: 1350). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Experimental studies have shown that this missense change affects SIAE function (PMID: 20555325). 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.

Autoimmune disease, susceptibility to, 6

Other:1

Jul 08, 2010

OMIM

Significance:risk factor

Review Status:no assertion criteria provided

Collection Method:literature only

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Pathogenic

0.17

BayesDel_noAF

Pathogenic

0.45

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

DEOGEN2

Pathogenic

0.89

Eigen

Pathogenic

0.80

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.93

M_CAP

Uncertain

0.20

MetaRNN

Uncertain

0.48

MetaSVM

Pathogenic

0.84

MutationAssessor

Pathogenic

3.1

PhyloP100

6.2

PrimateAI

Uncertain

0.51

PROVEAN

Pathogenic

-5.2

REVEL

Pathogenic

0.74

Sift

Benign

0.039

Sift4G

Uncertain

0.035

Polyphen

1.0

Vest4

0.87

MVP

0.82

MPC

0.62

ClinPred

0.070

GERP RS

5.5

Varity_R

0.31

gMVP

0.82

Mutation Taster

=15/85

disease causing

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over