Genetic Variant SIGLEC11:p.Ala595Thr (chr19-49951938-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_052884.3(SIGLEC11):c.1783G>A(p.Ala595Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000439 in 1,458,818 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000044 ( 0 hom. )

Consequence

SIGLEC11
NM_052884.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.367

Publications

0 publications found

Variant links:

Genes affected

SIGLEC11 (HGNC:15622): (sialic acid binding Ig like lectin 11) This gene encodes a member of the sialic acid-binding immunoglobulin-like lectin family. These cell surface lectins are characterized by structural motifs in the immunoglobulin (Ig)-like domains and sialic acid recognition sites in the first Ig V set domain. This family member mediates anti-inflammatory and immunosuppressive signaling. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

SIGLEC11 links:

ENSG00000269179 (HGNC:):

ENSG00000269179 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06664166).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052884.3. 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
	SIGLEC11	NM_052884.3	MANE Select	c.1783G>A	p.Ala595Thr	missense	Exon 10 of 11	NP_443116.2	Q96RL6-1
	SIGLEC11	NM_001135163.1		c.1495G>A	p.Ala499Thr	missense	Exon 9 of 10	NP_001128635.1	Q96RL6-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SIGLEC11	ENST00000447370.6	TSL:1 MANE Select	c.1783G>A	p.Ala595Thr	missense	Exon 10 of 11	ENSP00000412361.2	Q96RL6-1
SIGLEC11	ENST00000426971.2	TSL:1	c.1495G>A	p.Ala499Thr	missense	Exon 9 of 10	ENSP00000398891.2	Q96RL6-2
ENSG00000269179	ENST00000451973.1	TSL:2	n.*30G>A		non_coding_transcript_exon	Exon 2 of 3	ENSP00000391489.1	H7BZU6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000405

AC:

AN:

247116

AF XY:

0.00000748

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000892

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000439

AC:

AN:

1458818

Hom.:

Cov.:

AF XY:

0.0000469

AC XY:

AN XY:

725698

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33420

American (AMR)

AF:

0.00

AC:

AN:

44488

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25996

East Asian (EAS)

AF:

0.00

AC:

AN:

39552

South Asian (SAS)

AF:

0.00

AC:

AN:

85870

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52456

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.0000567

AC:

AN:

1111002

Other (OTH)

AF:

0.0000166

AC:

AN:

60278

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000189

ExAC

AF:

0.00000824

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.62

CADD

Benign

5.1

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.00093

Eigen

Benign

-0.95

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.027

LIST_S2

Benign

0.54

M_CAP

Benign

0.0025

MetaRNN

Benign

0.067

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.94

PhyloP100

0.37

PrimateAI

Benign

0.28

PROVEAN

Benign

0.37

REVEL

Benign

0.12

Sift

Benign

0.67

Sift4G

Benign

0.34

Polyphen

0.26

Vest4

0.23

MutPred

0.29

Gain of phosphorylation at A595 (P = 0.0236)

MVP

0.40

MPC

0.011

ClinPred

0.12

GERP RS

-1.1

Varity_R

0.047

gMVP

0.098

Mutation Taster

=98/2

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over