Variant chr11-124660768-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.265A>G(p.Met89Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0498 in 1,614,108 control chromosomes in the GnomAD database, including 2,336 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.037 ( 159 hom., cov: 32)

Exomes 𝑓: 0.051 ( 2177 hom. )

Consequence

SIAE
NM_170601.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2O:1

Conservation

PhyloP100: -0.0520

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0025379956).

BP6

Variant 11-124660768-T-C is Benign according to our data. Variant chr11-124660768-T-C is described in ClinVar as [Benign]. Clinvar id is 1352.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0563 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SIAE	NM_170601.5 linkuse as main transcript	c.265A>G	p.Met89Val	missense_variant	3/10	ENST00000263593.8
SIAE	NM_001199922.2 linkuse as main transcript	c.160A>G	p.Met54Val	missense_variant	5/12
SIAE	XM_047427133.1 linkuse as main transcript	c.265A>G	p.Met89Val	missense_variant	3/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SIAE	ENST00000263593.8 linkuse as main transcript	c.265A>G	p.Met89Val	missense_variant	3/10	1	NM_170601.5	P2	Q9HAT2-1

Frequencies

GnomAD3 genomes

AF:

0.0371

AC:

5648

AN:

152200

Hom.:

159

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00996

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.0250

Gnomad ASJ

AF:

0.0276

Gnomad EAS

AF:

0.00115

Gnomad SAS

AF:

0.0197

Gnomad FIN

AF:

0.0614

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0578

Gnomad OTH

AF:

0.0306

GnomAD3 exomes

AF:

0.0377

AC:

9478

AN:

251410

Hom.:

243

AF XY:

0.0385

AC XY:

5236

AN XY:

135862

show subpopulations

Gnomad AFR exome

AF:

0.00929

Gnomad AMR exome

AF:

0.0149

Gnomad ASJ exome

AF:

0.0249

Gnomad EAS exome

AF:

0.00125

Gnomad SAS exome

AF:

0.0230

Gnomad FIN exome

AF:

0.0626

Gnomad NFE exome

AF:

0.0548

Gnomad OTH exome

AF:

0.0401

GnomAD4 exome

AF:

0.0511

AC:

74660

AN:

1461790

Hom.:

2177

Cov.:

AF XY:

0.0503

AC XY:

36601

AN XY:

727198

show subpopulations

Gnomad4 AFR exome

AF:

0.00690

Gnomad4 AMR exome

AF:

0.0152

Gnomad4 ASJ exome

AF:

0.0249

Gnomad4 EAS exome

AF:

0.00197

Gnomad4 SAS exome

AF:

0.0256

Gnomad4 FIN exome

AF:

0.0651

Gnomad4 NFE exome

AF:

0.0580

Gnomad4 OTH exome

AF:

0.0447

GnomAD4 genome

AF:

0.0371

AC:

5648

AN:

152318

Hom.:

159

Cov.:

AF XY:

0.0372

AC XY:

2771

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.00994

Gnomad4 AMR

AF:

0.0250

Gnomad4 ASJ

AF:

0.0276

Gnomad4 EAS

AF:

0.00116

Gnomad4 SAS

AF:

0.0201

Gnomad4 FIN

AF:

0.0614

Gnomad4 NFE

AF:

0.0578

Gnomad4 OTH

AF:

0.0302

Alfa

AF:

0.0491

Hom.:

338

Bravo

AF:

0.0328

TwinsUK

AF:

0.0642

AC:

238

ALSPAC

AF:

0.0646

AC:

249

ESP6500AA

AF:

0.0114

AC:

ESP6500EA

AF:

0.0570

AC:

490

ExAC

AF:

0.0387

AC:

4698

Asia WGS

AF:

0.00722

AC:

AN:

3478

EpiCase

AF:

0.0513

EpiControl

AF:

0.0481

ClinVar

Significance: Benign

Submissions summary: Benign:2Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

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

Autoimmune disease, susceptibility to, 6

Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Jul 08, 2010

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.37

CADD

Benign

0.51

DANN

Benign

0.55

DEOGEN2

Benign

0.13

T;.;.

Eigen

Benign

-0.91

Eigen_PC

Benign

-0.82

FATHMM_MKL

Benign

0.070

LIST_S2

Benign

0.75

T;T;.

MetaRNN

Benign

0.0025

T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.84

L;.;.

MutationTaster

Benign

0.83

D;D

PrimateAI

Benign

0.25

PROVEAN

Benign

-1.4

N;N;.

REVEL

Benign

0.18

Sift

Benign

0.43

T;T;.

Sift4G

Benign

0.57

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.095

MPC

0.14

ClinPred

0.0012

GERP RS

-0.45

Varity_R

0.034

gMVP

0.48

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