11-124637071-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_170601.5(SIAE):c.1452G>A(p.Thr484Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.046 in 1,613,918 control chromosomes in the GnomAD database, including 7,215 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 3325 hom., cov: 32)

Exomes 𝑓: 0.037 ( 3890 hom. )

Consequence

SIAE
NM_170601.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.82

Publications

13 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

BP6

Variant 11-124637071-C-T is Benign according to our data. Variant chr11-124637071-C-T is described in ClinVar as [Benign]. Clinvar id is 1168498.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.82 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.386 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIAE	NM_170601.5 link	c.1452G>A	p.Thr484Thr	synonymous_variant	Exon 10 of 10	ENST00000263593.8	NP_733746.1	Q9HAT2-1
SIAE	NM_001199922.2 link	c.1347G>A	p.Thr449Thr	synonymous_variant	Exon 12 of 12		NP_001186851.1	Q9HAT2-2
SIAE	XM_047427132.1 link	c.879G>A	p.Thr293Thr	synonymous_variant	Exon 7 of 7		XP_047283088.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SIAE	ENST00000263593.8 link	c.1452G>A	p.Thr484Thr	synonymous_variant	Exon 10 of 10	1	NM_170601.5	ENSP00000263593.3	Q9HAT2-1
SIAE	ENST00000618733.4 link	c.1347G>A	p.Thr449Thr	synonymous_variant	Exon 12 of 12	1		ENSP00000478211.1	Q9HAT2-2
SIAE	ENST00000545756.5 link	c.1347G>A	p.Thr449Thr	synonymous_variant	Exon 11 of 11	5		ENSP00000437877.1	Q9HAT2-2

Frequencies

GnomAD3 genomes

AF:

0.130

AC:

19775

AN:

151908

Hom.:

3300

Cov.:

show subpopulations

Gnomad AFR

AF:

0.391

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0669

Gnomad ASJ

AF:

0.0369

Gnomad EAS

AF:

0.101

Gnomad SAS

AF:

0.0381

Gnomad FIN

AF:

0.00576

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.0223

Gnomad OTH

AF:

0.102

GnomAD2 exomes

AF:

0.0545

AC:

13706

AN:

251460

AF XY:

0.0472

show subpopulations

Gnomad AFR exome

AF:

0.405

Gnomad AMR exome

AF:

0.0338

Gnomad ASJ exome

AF:

0.0390

Gnomad EAS exome

AF:

0.102

Gnomad FIN exome

AF:

0.00513

Gnomad NFE exome

AF:

0.0207

Gnomad OTH exome

AF:

0.0391

GnomAD4 exome

AF:

0.0372

AC:

54455

AN:

1461890

Hom.:

3890

Cov.:

AF XY:

0.0361

AC XY:

26250

AN XY:

727246

show subpopulations

African (AFR)

AF:

0.409

AC:

13687

AN:

33480

American (AMR)

AF:

0.0381

AC:

1706

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0403

AC:

1052

AN:

26136

East Asian (EAS)

AF:

0.137

AC:

5420

AN:

39700

South Asian (SAS)

AF:

0.0348

AC:

2999

AN:

86258

European-Finnish (FIN)

AF:

0.00648

AC:

346

AN:

53420

Middle Eastern (MID)

AF:

0.0319

AC:

184

AN:

5768

European-Non Finnish (NFE)

AF:

0.0229

AC:

25479

AN:

1112008

Other (OTH)

AF:

0.0593

AC:

3582

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

3362

6724

10086

13448

16810

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.131

AC:

19850

AN:

152028

Hom.:

3325

Cov.:

AF XY:

0.126

AC XY:

9371

AN XY:

74326

show subpopulations

African (AFR)

AF:

0.391

AC:

16192

AN:

41368

American (AMR)

AF:

0.0667

AC:

1020

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0369

AC:

128

AN:

3466

East Asian (EAS)

AF:

0.101

AC:

521

AN:

5152

South Asian (SAS)

AF:

0.0378

AC:

182

AN:

4820

European-Finnish (FIN)

AF:

0.00576

AC:

AN:

10594

Middle Eastern (MID)

AF:

0.0510

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0223

AC:

1519

AN:

68014

Other (OTH)

AF:

0.100

AC:

212

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

660

1321

1981

2642

3302

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0591

Hom.:

3735

Bravo

AF:

0.148

Asia WGS

AF:

0.121

AC:

421

AN:

3478

EpiCase

AF:

0.0234

EpiControl

AF:

0.0225

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

SIAE-related disorder

Benign:1

Nov 14, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

0.12

(source)

DANN

Benign

0.81

PhyloP100

-1.8

Mutation Taster

=96/4

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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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11-124637071-C-T

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