Variant rs78778622 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000263593.8(SIAE):c.265A>T(p.Met89Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,856 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M89V) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SIAE
ENST00000263593.8 missense

Scores

Clinical Significance

Not reported in ClinVar

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08963266).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SIAE	NM_170601.5 linkuse as main transcript	c.265A>T	p.Met89Leu	missense_variant	3/10	ENST00000263593.8	NP_733746.1
SIAE	NM_001199922.2 linkuse as main transcript	c.160A>T	p.Met54Leu	missense_variant	5/12		NP_001186851.1
SIAE	XM_047427133.1 linkuse as main transcript	c.265A>T	p.Met89Leu	missense_variant	3/5		XP_047283089.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SIAE	ENST00000263593.8 linkuse as main transcript	c.265A>T	p.Met89Leu	missense_variant	3/10	1	NM_170601.5	ENSP00000263593	P2	Q9HAT2-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251410

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135862

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461856

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727224

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.011

BayesDel_noAF

Benign

-0.25

CADD

Benign

DANN

Benign

0.81

DEOGEN2

Benign

0.13

T;.;.

Eigen

Benign

-0.94

Eigen_PC

Benign

-0.85

FATHMM_MKL

Benign

0.25

LIST_S2

Uncertain

0.86

D;D;.

M_CAP

Benign

0.019

MetaRNN

Benign

0.090

T;T;T

MetaSVM

Benign

-0.76

MutationAssessor

Benign

1.7

L;.;.

MutationTaster

Benign

0.80

D;D

PrimateAI

Benign

0.27

PROVEAN

Benign

-1.4

N;N;.

REVEL

Benign

0.26

Sift

Benign

0.13

T;T;.

Sift4G

Benign

0.63

T;T;T

Polyphen

0.0020

B;B;B

Vest4

0.32

MutPred

0.42

Loss of catalytic residue at V85 (P = 0.0276);.;.;

MVP

0.25

MPC

0.13

ClinPred

0.040

GERP RS

-0.45

Varity_R

0.073

gMVP

0.48

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over