Variant 11-124637071-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_170601.5(SIAE):c.1452G>A(p.Thr484=) 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

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 -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/exons	MANE	Protein
SIAE	NM_170601.5 linkuse as main transcript	c.1452G>A	p.Thr484=	synonymous_variant	10/10	ENST00000263593.8	NP_733746.1
SIAE	NM_001199922.2 linkuse as main transcript	c.1347G>A	p.Thr449=	synonymous_variant	12/12		NP_001186851.1
SIAE	XM_047427132.1 linkuse as main transcript	c.879G>A	p.Thr293=	synonymous_variant	7/7		XP_047283088.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SIAE	ENST00000263593.8 linkuse as main transcript	c.1452G>A	p.Thr484=	synonymous_variant	10/10	1	NM_170601.5	ENSP00000263593	P2	Q9HAT2-1
SIAE	ENST00000618733.4 linkuse as main transcript	c.1347G>A	p.Thr449=	synonymous_variant	12/12	1		ENSP00000478211	A2	Q9HAT2-2
SIAE	ENST00000545756.5 linkuse as main transcript	c.1347G>A	p.Thr449=	synonymous_variant	11/11	5		ENSP00000437877	A2	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

GnomAD3 exomes

AF:

0.0545

AC:

13706

AN:

251460

Hom.:

1542

AF XY:

0.0472

AC XY:

6420

AN XY:

135902

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 SAS exome

AF:

0.0318

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

Gnomad4 AFR exome

AF:

0.409

Gnomad4 AMR exome

AF:

0.0381

Gnomad4 ASJ exome

AF:

0.0403

Gnomad4 EAS exome

AF:

0.137

Gnomad4 SAS exome

AF:

0.0348

Gnomad4 FIN exome

AF:

0.00648

Gnomad4 NFE exome

AF:

0.0229

Gnomad4 OTH exome

AF:

0.0593

GnomAD4 genome

AF:

0.131

AC:

19850

AN:

152028

Hom.:

3325

Cov.:

AF XY:

0.126

AC XY:

9371

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.391

Gnomad4 AMR

AF:

0.0667

Gnomad4 ASJ

AF:

0.0369

Gnomad4 EAS

AF:

0.101

Gnomad4 SAS

AF:

0.0378

Gnomad4 FIN

AF:

0.00576

Gnomad4 NFE

AF:

0.0223

Gnomad4 OTH

AF:

0.100

Alfa

AF:

0.0474

Hom.:

1045

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

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	- -

SIAE-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 14, 2019

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

DANN

Benign

0.81

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

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