Variant 11-124669377-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

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

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 links:

SIAE (HGNC:):

SIAE links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
SIAE	NM_170601.5 linkuse as main transcript	c.212A>G	p.Lys71Arg	missense_variant	2/10	ENST00000263593.8	NP_733746.1	Q9HAT2-1
SIAE	NM_001199922.2 linkuse as main transcript	c.107A>G	p.Lys36Arg	missense_variant	4/12		NP_001186851.1	Q9HAT2-2
SIAE	XM_047427133.1 linkuse as main transcript	c.212A>G	p.Lys71Arg	missense_variant	2/5		XP_047283089.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SIAE	ENST00000263593.8 linkuse as main transcript	c.212A>G	p.Lys71Arg	missense_variant	2/10	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

GnomAD3 exomes

AF:

0.0311

AC:

7831

AN:

251468

Hom.:

640

AF XY:

0.0268

AC XY:

3645

AN XY:

135908

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 SAS exome

AF:

0.0235

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

Gnomad4 AFR exome

AF:

0.244

Gnomad4 AMR exome

AF:

0.0165

Gnomad4 ASJ exome

AF:

0.0241

Gnomad4 EAS exome

AF:

0.141

Gnomad4 SAS exome

AF:

0.0248

Gnomad4 FIN exome

AF:

0.00373

Gnomad4 NFE exome

AF:

0.00132

Gnomad4 OTH exome

AF:

0.0286

GnomAD4 genome

AF:

0.0732

AC:

11149

AN:

152206

Hom.:

1159

Cov.:

AF XY:

0.0724

AC XY:

5388

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.231

Gnomad4 AMR

AF:

0.0318

Gnomad4 ASJ

AF:

0.0202

Gnomad4 EAS

AF:

0.107

Gnomad4 SAS

AF:

0.0311

Gnomad4 FIN

AF:

0.00433

Gnomad4 NFE

AF:

0.00206

Gnomad4 OTH

AF:

0.0544

Alfa

AF:

0.0231

Hom.:

551

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

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

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;.;.

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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over