rs12282107

Variant names:

• chr11-124669377-T-C
• rs12282107
• NM_170601.5:c.212A>G

Variant summary

Our verdict is Benign. The variant received -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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• 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
• Publications: 27 publications found

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 Gene-Disease associations (from GenCC):

• autoimmune disease, susceptibility to, 6

  Inheritance: Unknown Classification: LIMITED Submitted by: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_170601.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIAE	NM_170601.5	MANE Select	c.212A>G	p.Lys71Arg	missense	Exon 2 of 10	NP_733746.1	Q9HAT2-1
	SIAE	NM_001199922.2		c.107A>G	p.Lys36Arg	missense	Exon 4 of 12	NP_001186851.1	Q9HAT2-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIAE	ENST00000263593.8	TSL:1 MANE Select	c.212A>G	p.Lys71Arg	missense	Exon 2 of 10	ENSP00000263593.3	Q9HAT2-1
	SIAE	ENST00000618733.4	TSL:1	c.107A>G	p.Lys36Arg	missense	Exon 4 of 12	ENSP00000478211.1	Q9HAT2-2
	SIAE	ENST00000436137.2	TSL:1	n.325A>G		non_coding_transcript_exon	Exon 2 of 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

GnomAD2 exomes AF: 0.0311 AC: 7831 AN: 251468 AF XY: 0.0268

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 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

African (AFR) AF: 0.244 AC: 8171 AN: 33474

American (AMR) AF: 0.0165 AC: 737 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0241 AC: 630 AN: 26134

East Asian (EAS) AF: 0.141 AC: 5612 AN: 39698

South Asian (SAS) AF: 0.0248 AC: 2143 AN: 86250

European-Finnish (FIN) AF: 0.00373 AC: 199 AN: 53418

Middle Eastern (MID) AF: 0.0165 AC: 95 AN: 5768

European-Non Finnish (NFE) AF: 0.00132 AC: 1469 AN: 1111996

Other (OTH) AF: 0.0286 AC: 1729 AN: 60388

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

African (AFR) AF: 0.231 AC: 9584 AN: 41488

American (AMR) AF: 0.0318 AC: 487 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0202 AC: 70 AN: 3472

East Asian (EAS) AF: 0.107 AC: 551 AN: 5168

South Asian (SAS) AF: 0.0311 AC: 150 AN: 4822

European-Finnish (FIN) AF: 0.00433 AC: 46 AN: 10614

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.00206 AC: 140 AN: 68024

Other (OTH) AF: 0.0544 AC: 115 AN: 2114

Alfa AF: 0.0268 Hom.: 902

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

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
MetaRNN	Benign	0.0014	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		3.5
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.24
Sift	Benign	0.11	T
Sift4G	Benign	0.26	T
Polyphen		0.077	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
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12282107; hg19: chr11-124539273; COSMIC: COSV108732328; COSMIC: COSV108732328;