rs12282107

Positions:

• chr11-124669377-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_170601.5(SIAE):​c.212A>G​(p.Lys71Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0198 in 1,614,052 control chromosomes in the GnomAD database, including 2,735 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.073 (1159 hom., cov: 32)
  • Exomes 𝑓: 0.014 (1576 hom.)
• Consequence: SIAE NM_170601.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 3.48

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0014370382).
• BP6: Variant 11-124669377-T-C is Benign according to our data. Variant chr11-124669377-T-C is described in ClinVar as [Benign]. Clinvar id is 1168500.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.227 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SIAE	NM_170601.5	c.212A>G	p.Lys71Arg	missense_variant	2/10	ENST00000263593.8	NP_733746.1
SIAE	NM_001199922.2	c.107A>G	p.Lys36Arg	missense_variant	4/12		NP_001186851.1
SIAE	XM_047427133.1	c.212A>G	p.Lys71Arg	missense_variant	2/5		XP_047283089.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SIAE	ENST00000263593.8	c.212A>G	p.Lys71Arg	missense_variant	2/10	1	NM_170601.5	ENSP00000263593.3

Frequencies

GnomAD3 genomes AF: 0.0732 AC: 11130 AN: 152090 Hom.: 1155 Cov.: 32

Gnomad AFR AF: 0.231

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0320

Gnomad ASJ AF: 0.0202

Gnomad EAS AF: 0.106

Gnomad SAS AF: 0.0315

Gnomad FIN AF: 0.00433

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.00206

Gnomad OTH AF: 0.0554

GnomAD3 exomes AF: 0.0311 AC: 7831 AN: 251468 Hom.: 640 AF XY: 0.0268 AC XY: 3645 AN XY: 135908

Gnomad AFR exome AF: 0.244

Gnomad AMR exome AF: 0.0146

Gnomad ASJ exome AF: 0.0236

Gnomad EAS exome AF: 0.108

Gnomad SAS exome AF: 0.0235

Gnomad FIN exome AF: 0.00416

Gnomad NFE exome AF: 0.00185

Gnomad OTH exome AF: 0.0182

GnomAD4 exome AF: 0.0142 AC: 20785 AN: 1461846 Hom.: 1576 Cov.: 32 AF XY: 0.0140 AC XY: 10151 AN XY: 727236

Gnomad4 AFR exome AF: 0.244

Gnomad4 AMR exome AF: 0.0165

Gnomad4 ASJ exome AF: 0.0241

Gnomad4 EAS exome AF: 0.141

Gnomad4 SAS exome AF: 0.0248

Gnomad4 FIN exome AF: 0.00373

Gnomad4 NFE exome AF: 0.00132

Gnomad4 OTH exome AF: 0.0286

GnomAD4 genome AF: 0.0732 AC: 11149 AN: 152206 Hom.: 1159 Cov.: 32 AF XY: 0.0724 AC XY: 5388 AN XY: 74424

Gnomad4 AFR AF: 0.231

Gnomad4 AMR AF: 0.0318

Gnomad4 ASJ AF: 0.0202

Gnomad4 EAS AF: 0.107

Gnomad4 SAS AF: 0.0311

Gnomad4 FIN AF: 0.00433

Gnomad4 NFE AF: 0.00206

Gnomad4 OTH AF: 0.0544

Alfa AF: 0.0231 Hom.: 551

Bravo AF: 0.0838

TwinsUK AF: 0.00189 AC: 7

ALSPAC AF: 0.000778 AC: 3

ESP6500AA AF: 0.221 AC: 973

ESP6500EA AF: 0.00198 AC: 17

ExAC AF: 0.0347 AC: 4209

Asia WGS AF: 0.0940 AC: 327 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

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

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.16	T;.;.
Eigen	Benign	-0.046
Eigen_PC	Benign	0.078
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.67	T;T;.
MetaRNN	Benign	0.0014	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.8	M;.;.
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-1.2	N;N;.
REVEL	Benign	0.24
Sift	Benign	0.11	T;T;.
Sift4G	Benign	0.26	T;T;T
Polyphen		0.077	B;B;B
Vest4		0.14
MPC		0.11
ClinPred		0.039	T
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.081
gMVP		0.51

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

Other links and lift over

dbSNP: rs12282107; hg19: chr11-124539273;