rs201877149

Variant names:

• chr11-124638651-A-G
• rs201877149
• NM_170601.5:c.1211T>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_170601.5(SIAE):​c.1211T>C​(p.Phe404Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000112 in 1,614,000 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.00022 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00010 (0 hom.)
• Consequence: SIAE NM_170601.5 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2 O:1
• Conservation: PhyloP100: 4.71
• Publications: 9 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: Uncertain_significance. The variant received 0 ACMG points.

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.1211T>C	p.Phe404Ser	missense	Exon 9 of 10	NP_733746.1	Q9HAT2-1
	SIAE	NM_001199922.2		c.1106T>C	p.Phe369Ser	missense	Exon 11 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.1211T>C	p.Phe404Ser	missense	Exon 9 of 10	ENSP00000263593.3	Q9HAT2-1
	SIAE	ENST00000618733.4	TSL:1	c.1106T>C	p.Phe369Ser	missense	Exon 11 of 12	ENSP00000478211.1	Q9HAT2-2
	SIAE	ENST00000899891.1		c.1202T>C	p.Phe401Ser	missense	Exon 9 of 10	ENSP00000569950.1

Frequencies

GnomAD3 genomes AF: 0.000217 AC: 33 AN: 152120 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000590

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000171 AC: 43 AN: 251456 AF XY: 0.000162

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000318

Gnomad ASJ exome AF: 0.00179

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000105

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.000101 AC: 147 AN: 1461880 Hom.: 0 Cov.: 31 AF XY: 0.000103 AC XY: 75 AN XY: 727244

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.000179 AC: 8 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00180 AC: 47 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.0000665 AC: 74 AN: 1112000

Other (OTH) AF: 0.000265 AC: 16 AN: 60396

GnomAD4 genome AF: 0.000217 AC: 33 AN: 152120 Hom.: 0 Cov.: 32 AF XY: 0.000256 AC XY: 19 AN XY: 74306

African (AFR) AF: 0.0000241 AC: 1 AN: 41414

American (AMR) AF: 0.000590 AC: 9 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.00346 AC: 12 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.000234 Hom.: 1

Bravo AF: 0.000219

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.000107 AC: 13

EpiCase AF: 0.000218

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)
-	1	-	not specified (1)
-	-	-	Autoimmune disease, susceptibility to, 6 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Pathogenic	0.32
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.50	T
Eigen	Benign	0.070
Eigen_PC	Benign	0.18
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.041	D
MetaRNN	Uncertain	0.69	D
MetaSVM	Benign	-0.45	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		4.7
PrimateAI	Uncertain	0.57	T
PROVEAN	Pathogenic	-5.8	D
REVEL	Uncertain	0.63
Sift	Benign	0.054	T
Sift4G	Benign	0.10	T
Polyphen		0.44	B
Vest4		0.95
MVP		0.63
MPC		0.57
ClinPred		0.84	D
GERP RS		4.3
Varity_R		0.47
gMVP		0.86
Mutation Taster		=20/80	disease causing

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: rs201877149; hg19: chr11-124508547;