rs7941523

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -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. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

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

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=0.0026714504).

BP6

Variant 11-124637123-G-A is Benign according to our data. Variant chr11-124637123-G-A is described in ClinVar as [Benign]. Clinvar id 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

GnomAD3 exomes

AF:

0.00870

AC:

2187

AN:

251472

Hom.:

AF XY:

0.00764

AC XY:

1039

AN XY:

135910

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 SAS exome

AF:

0.0113

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

Gnomad4 AFR exome

AF:

0.0782

Gnomad4 AMR exome

AF:

0.00624

Gnomad4 ASJ exome

AF:

0.00784

Gnomad4 EAS exome

AF:

0.0134

Gnomad4 SAS exome

AF:

0.0115

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000417

Gnomad4 OTH exome

AF:

0.00868

GnomAD4 genome

AF:

0.0223

AC:

3401

AN:

152212

Hom.:

109

Cov.:

AF XY:

0.0219

AC XY:

1626

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.0722

Gnomad4 AMR

AF:

0.0118

Gnomad4 ASJ

AF:

0.00778

Gnomad4 EAS

AF:

0.00988

Gnomad4 SAS

AF:

0.0126

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000573

Gnomad4 OTH

AF:

0.0180

Alfa

AF:

0.00622

Hom.:

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

- -

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) -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

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;.;.

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

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

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