rs1942663

Variant names:

• chr11-124654731-A-G
• rs1942663
• NM_170601.5:c.468T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The ENST00000263593.8(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 (★★). Synonymous variant affecting the same amino acid position (i.e. S156S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.18 (6287 hom., cov: 32)
  • Exomes 𝑓: 0.043 (6671 hom.)
• Consequence: SIAE ENST00000263593.8 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -3.20
• Publications: 10 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: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000263593.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIAE	NM_170601.5	MANE Select	c.468T>C	p.Ser156Ser	synonymous	Exon 4 of 10	NP_733746.1
	SIAE	NM_001199922.2		c.363T>C	p.Ser121Ser	synonymous	Exon 6 of 12	NP_001186851.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIAE	ENST00000263593.8	TSL:1 MANE Select	c.468T>C	p.Ser156Ser	synonymous	Exon 4 of 10	ENSP00000263593.3
	SIAE	ENST00000618733.4	TSL:1	c.363T>C	p.Ser121Ser	synonymous	Exon 6 of 12	ENSP00000478211.1
	SIAE	ENST00000545756.5	TSL:5	c.363T>C	p.Ser121Ser	synonymous	Exon 5 of 11	ENSP00000437877.1

Frequencies

GnomAD3 genomes AF: 0.175 AC: 26539 AN: 151928 Hom.: 6250 Cov.: 32

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

GnomAD2 exomes AF: 0.0667 AC: 16780 AN: 251472 AF XY: 0.0564

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 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.: 33 AF XY: 0.0408 AC XY: 29648 AN XY: 727236

African (AFR) AF: 0.566 AC: 18953 AN: 33478

American (AMR) AF: 0.0478 AC: 2139 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0456 AC: 1193 AN: 26136

East Asian (EAS) AF: 0.138 AC: 5497 AN: 39700

South Asian (SAS) AF: 0.0361 AC: 3112 AN: 86256

European-Finnish (FIN) AF: 0.00996 AC: 532 AN: 53420

Middle Eastern (MID) AF: 0.0418 AC: 241 AN: 5760

European-Non Finnish (NFE) AF: 0.0237 AC: 26390 AN: 1112000

Other (OTH) AF: 0.0714 AC: 4313 AN: 60392

GnomAD4 genome AF: 0.175 AC: 26632 AN: 152046 Hom.: 6287 Cov.: 32 AF XY: 0.170 AC XY: 12622 AN XY: 74334

African (AFR) AF: 0.542 AC: 22414 AN: 41370

American (AMR) AF: 0.0872 AC: 1333 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0410 AC: 142 AN: 3466

East Asian (EAS) AF: 0.102 AC: 529 AN: 5164

South Asian (SAS) AF: 0.0388 AC: 187 AN: 4820

European-Finnish (FIN) AF: 0.00979 AC: 104 AN: 10618

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0236 AC: 1606 AN: 68016

Other (OTH) AF: 0.141 AC: 297 AN: 2110

Alfa AF: 0.0790 Hom.: 3210

Bravo AF: 0.199

Asia WGS AF: 0.136 AC: 473 AN: 3478

EpiCase AF: 0.0248

EpiControl AF: 0.0239

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	SIAE-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.087
DANN	Benign	0.43
PhyloP100		-3.2
Mutation Taster		=100/0	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: rs1942663; hg19: chr11-124524627; COSMIC: COSV55015429; COSMIC: COSV55015429;