11-124637123-G-A

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.1400C>T(p.Ala467Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00561 in 1,614,100 control chromosomes in the GnomAD database, including 227 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.022 ( 109 hom., cov: 32)

Exomes 𝑓: 0.0039 ( 118 hom. )

Consequence

SIAE
NM_170601.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.690

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0026714504).

BP6

Variant 11-124637123-G-A is Benign according to our data. Variant chr11-124637123-G-A is described in ClinVar as Benign. ClinVar VariationId is 776676.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0701 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIAE	NM_170601.5 link	c.1400C>T	p.Ala467Val	missense_variant	Exon 10 of 10	ENST00000263593.8	NP_733746.1	Q9HAT2-1
SIAE	NM_001199922.2 link	c.1295C>T	p.Ala432Val	missense_variant	Exon 12 of 12		NP_001186851.1	Q9HAT2-2
SIAE	XM_047427132.1 link	c.827C>T	p.Ala276Val	missense_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.1400C>T	p.Ala467Val	missense_variant	Exon 10 of 10	1	NM_170601.5	ENSP00000263593.3	Q9HAT2-1
SIAE	ENST00000618733.4 link	c.1295C>T	p.Ala432Val	missense_variant	Exon 12 of 12	1		ENSP00000478211.1	Q9HAT2-2
SIAE	ENST00000545756.5 link	c.1295C>T	p.Ala432Val	missense_variant	Exon 11 of 11	5		ENSP00000437877.1	Q9HAT2-2

Frequencies

GnomAD3 genomes

AF:

0.0223

AC:

3390

AN:

152094

Hom.:

109

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0721

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0118

Gnomad ASJ

AF:

0.00778

Gnomad EAS

AF:

0.00986

Gnomad SAS

AF:

0.0130

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.000573

Gnomad OTH

AF:

0.0182

GnomAD2 exomes

AF:

0.00870

AC:

2187

AN:

251472

AF XY:

0.00764

show subpopulations

Gnomad AFR exome

AF:

0.0780

Gnomad AMR exome

AF:

0.00558

Gnomad ASJ exome

AF:

0.00714

Gnomad EAS exome

AF:

0.0111

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000598

Gnomad OTH exome

AF:

0.00587

GnomAD4 exome

AF:

0.00387

AC:

5656

AN:

1461888

Hom.:

118

Cov.:

AF XY:

0.00388

AC XY:

2819

AN XY:

727244

show subpopulations

African (AFR)

AF:

0.0782

AC:

2619

AN:

33476

American (AMR)

AF:

0.00624

AC:

279

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00784

AC:

205

AN:

26136

East Asian (EAS)

AF:

0.0134

AC:

531

AN:

39700

South Asian (SAS)

AF:

0.0115

AC:

996

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00659

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000417

AC:

464

AN:

1112010

Other (OTH)

AF:

0.00868

AC:

524

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.454

Heterozygous variant carriers

369

738

1108

1477

1846

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

240

360

480

600

<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:

0.0223

AC:

3401

AN:

152212

Hom.:

109

Cov.:

AF XY:

0.0219

AC XY:

1626

AN XY:

74408

show subpopulations

African (AFR)

AF:

0.0722

AC:

2999

AN:

41520

American (AMR)

AF:

0.0118

AC:

181

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00778

AC:

AN:

3472

East Asian (EAS)

AF:

0.00988

AC:

AN:

5160

South Asian (SAS)

AF:

0.0126

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000573

AC:

AN:

68010

Other (OTH)

AF:

0.0180

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

156

312

468

624

780

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

102

136

170

<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:

0.00971

Hom.:

111

Bravo

AF:

0.0261

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.0666

AC:

293

ESP6500EA

AF:

0.000582

AC:

ExAC

AF:

0.00985

AC:

1196

Asia WGS

AF:

0.0240

AC:

AN:

3478

EpiCase

AF:

0.000763

EpiControl

AF:

0.000889

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

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

- -

Jul 15, 2020

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 24748456) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.096

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.52

CADD

Benign

7.4

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.067

T;.;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.046

LIST_S2

Benign

0.61

T;T;.

MetaRNN

Benign

0.0027

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

N;.;.

PhyloP100

-0.69

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.88

N;N;.

REVEL

Benign

0.14

Sift

Benign

0.37

T;T;.

Sift4G

Benign

0.31

T;T;T

Polyphen

0.11

B;.;.

Vest4

0.066

MVP

0.21

MPC

0.14

ClinPred

0.00068

GERP RS

-0.69

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.015

gMVP

0.34

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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