dbSNP rs1942663: SIAE:p.Ser156Ser (chr11-124654731-A-G) – ACMG Classification: Benign (-21 pts)

Variant summary

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

The NM_170601.5(SIAE):c.468T>C(p.Ser156Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0551 in 1,613,912 control chromosomes in the GnomAD database, including 12,958 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.18 ( 6287 hom., cov: 32)

Exomes 𝑓: 0.043 ( 6671 hom. )

Consequence

SIAE
NM_170601.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -3.20

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 11-124654731-A-G is Benign according to our data. Variant chr11-124654731-A-G is described in ClinVar as [Benign]. Clinvar id is 1168499.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.2 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.536 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIAE	NM_170601.5 link	c.468T>C	p.Ser156Ser	synonymous_variant	Exon 4 of 10	ENST00000263593.8	NP_733746.1	Q9HAT2-1
SIAE	NM_001199922.2 link	c.363T>C	p.Ser121Ser	synonymous_variant	Exon 6 of 12		NP_001186851.1	Q9HAT2-2
SIAE	XM_047427133.1 link	c.468T>C	p.Ser156Ser	synonymous_variant	Exon 4 of 5		XP_047283089.1
SIAE	XM_047427132.1 link	c.-2946T>C		upstream_gene_variant			XP_047283088.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SIAE	ENST00000263593.8 link	c.468T>C	p.Ser156Ser	synonymous_variant	Exon 4 of 10	1	NM_170601.5	ENSP00000263593.3	Q9HAT2-1
SIAE	ENST00000618733.4 link	c.363T>C	p.Ser121Ser	synonymous_variant	Exon 6 of 12	1		ENSP00000478211.1	Q9HAT2-2
SIAE	ENST00000545756.5 link	c.363T>C	p.Ser121Ser	synonymous_variant	Exon 5 of 11	5		ENSP00000437877.1	Q9HAT2-2
SIAE	ENST00000533613.1 link	n.492T>C		non_coding_transcript_exon_variant	Exon 3 of 3	4

Frequencies

GnomAD3 genomes

AF:

0.175

AC:

26539

AN:

151928

Hom.:

6250

Cov.:

show subpopulations

Gnomad AFR

AF:

0.541

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0874

Gnomad ASJ

AF:

0.0410

Gnomad EAS

AF:

0.102

Gnomad SAS

AF:

0.0392

Gnomad FIN

AF:

0.00979

Gnomad MID

AF:

0.0665

Gnomad NFE

AF:

0.0236

Gnomad OTH

AF:

0.143

GnomAD3 exomes

AF:

0.0667

AC:

16780

AN:

251472

Hom.:

2721

AF XY:

0.0564

AC XY:

7660

AN XY:

135908

show subpopulations

Gnomad AFR exome

AF:

0.555

Gnomad AMR exome

AF:

0.0422

Gnomad ASJ exome

AF:

0.0436

Gnomad EAS exome

AF:

0.103

Gnomad SAS exome

AF:

0.0332

Gnomad FIN exome

AF:

0.00878

Gnomad NFE exome

AF:

0.0218

Gnomad OTH exome

AF:

0.0453

GnomAD4 exome

AF:

0.0427

AC:

62370

AN:

1461866

Hom.:

6671

Cov.:

AF XY:

0.0408

AC XY:

29648

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.566

Gnomad4 AMR exome

AF:

0.0478

Gnomad4 ASJ exome

AF:

0.0456

Gnomad4 EAS exome

AF:

0.138

Gnomad4 SAS exome

AF:

0.0361

Gnomad4 FIN exome

AF:

0.00996

Gnomad4 NFE exome

AF:

0.0237

Gnomad4 OTH exome

AF:

0.0714

GnomAD4 genome

AF:

0.175

AC:

26632

AN:

152046

Hom.:

6287

Cov.:

AF XY:

0.170

AC XY:

12622

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.542

Gnomad4 AMR

AF:

0.0872

Gnomad4 ASJ

AF:

0.0410

Gnomad4 EAS

AF:

0.102

Gnomad4 SAS

AF:

0.0388

Gnomad4 FIN

AF:

0.00979

Gnomad4 NFE

AF:

0.0236

Gnomad4 OTH

AF:

0.141

Alfa

AF:

0.0627

Hom.:

1869

Bravo

AF:

0.199

Asia WGS

AF:

0.136

AC:

473

AN:

3478

EpiCase

AF:

0.0248

EpiControl

AF:

0.0239

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

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

- -

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

-0.93

CADD

Benign

0.087

DANN

Benign

0.43

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