rs12282107

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_170601.5(SIAE):c.212A>G(p.Lys71Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0198 in 1,614,052 control chromosomes in the GnomAD database, including 2,735 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.073 ( 1159 hom., cov: 32)

Exomes 𝑓: 0.014 ( 1576 hom. )

Consequence

SIAE
NM_170601.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.48

Publications

27 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: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0014370382).

BP6

Variant 11-124669377-T-C is Benign according to our data. Variant chr11-124669377-T-C is described in ClinVar as [Benign]. Clinvar id is 1168500.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.227 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIAE	NM_170601.5 link	c.212A>G	p.Lys71Arg	missense_variant	Exon 2 of 10	ENST00000263593.8	NP_733746.1	Q9HAT2-1
SIAE	NM_001199922.2 link	c.107A>G	p.Lys36Arg	missense_variant	Exon 4 of 12		NP_001186851.1	Q9HAT2-2
SIAE	XM_047427133.1 link	c.212A>G	p.Lys71Arg	missense_variant	Exon 2 of 5		XP_047283089.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIAE	ENST00000263593.8 link	c.212A>G	p.Lys71Arg	missense_variant	Exon 2 of 10	1	NM_170601.5	ENSP00000263593.3		Q9HAT2-1

Frequencies

GnomAD3 genomes

AF:

0.0732

AC:

11130

AN:

152090

Hom.:

1155

Cov.:

show subpopulations

Gnomad AFR

AF:

0.231

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0320

Gnomad ASJ

AF:

0.0202

Gnomad EAS

AF:

0.106

Gnomad SAS

AF:

0.0315

Gnomad FIN

AF:

0.00433

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.00206

Gnomad OTH

AF:

0.0554

GnomAD2 exomes

AF:

0.0311

AC:

7831

AN:

251468

AF XY:

0.0268

show subpopulations

Gnomad AFR exome

AF:

0.244

Gnomad AMR exome

AF:

0.0146

Gnomad ASJ exome

AF:

0.0236

Gnomad EAS exome

AF:

0.108

Gnomad FIN exome

AF:

0.00416

Gnomad NFE exome

AF:

0.00185

Gnomad OTH exome

AF:

0.0182

GnomAD4 exome

AF:

0.0142

AC:

20785

AN:

1461846

Hom.:

1576

Cov.:

AF XY:

0.0140

AC XY:

10151

AN XY:

727236

show subpopulations

African (AFR)

AF:

0.244

AC:

8171

AN:

33474

American (AMR)

AF:

0.0165

AC:

737

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.0241

AC:

630

AN:

26134

East Asian (EAS)

AF:

0.141

AC:

5612

AN:

39698

South Asian (SAS)

AF:

0.0248

AC:

2143

AN:

86250

European-Finnish (FIN)

AF:

0.00373

AC:

199

AN:

53418

Middle Eastern (MID)

AF:

0.0165

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00132

AC:

1469

AN:

1111996

Other (OTH)

AF:

0.0286

AC:

1729

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

1116

2232

3348

4464

5580

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

364

728

1092

1456

1820

<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:

0.0732

AC:

11149

AN:

152206

Hom.:

1159

Cov.:

AF XY:

0.0724

AC XY:

5388

AN XY:

74424

show subpopulations

African (AFR)

AF:

0.231

AC:

9584

AN:

41488

American (AMR)

AF:

0.0318

AC:

487

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0202

AC:

AN:

3472

East Asian (EAS)

AF:

0.107

AC:

551

AN:

5168

South Asian (SAS)

AF:

0.0311

AC:

150

AN:

4822

European-Finnish (FIN)

AF:

0.00433

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00206

AC:

140

AN:

68024

Other (OTH)

AF:

0.0544

AC:

115

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

428

856

1285

1713

2141

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

220

330

440

550

<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:

0.0268

Hom.:

902

Bravo

AF:

0.0838

TwinsUK

AF:

0.00189

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.221

AC:

973

ESP6500EA

AF:

0.00198

AC:

ExAC

AF:

0.0347

AC:

4209

Asia WGS

AF:

0.0940

AC:

327

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.30

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.16

T;.;.

Eigen

Benign

-0.046

Eigen_PC

Benign

0.078

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.67

T;T;.

MetaRNN

Benign

0.0014

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.8

M;.;.

PhyloP100

3.5

PrimateAI

Benign

0.45

PROVEAN

Benign

-1.2

N;N;.

REVEL

Benign

0.24

Sift

Benign

0.11

T;T;.

Sift4G

Benign

0.26

T;T;T

Polyphen

0.077

B;B;B

Vest4

0.14

MPC

0.11

ClinPred

0.039

GERP RS

4.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.081

gMVP

0.51

Mutation Taster

=98/2

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over