dbSNP rs140702198: SIGLEC11:p.Val581Leu (chr19-49952305-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_052884.3(SIGLEC11):c.1741G>C(p.Val581Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000287 in 1,612,558 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V581I) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00029 ( 1 hom. )

Consequence

SIGLEC11
NM_052884.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.05

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 made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0058817565).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIGLEC11	NM_052884.3 link	c.1741G>C	p.Val581Leu	missense_variant	Exon 9 of 11	ENST00000447370.6	NP_443116.2	Q96RL6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SIGLEC11	ENST00000447370.6 link	c.1741G>C	p.Val581Leu	missense_variant	Exon 9 of 11	1	NM_052884.3	ENSP00000412361.2	Q96RL6-1
SIGLEC11	ENST00000426971.2 link	c.1453G>C	p.Val485Leu	missense_variant	Exon 8 of 10	1		ENSP00000398891.2	Q96RL6-2
ENSG00000269179	ENST00000451973.1 link	n.110-333G>C		intron_variant	Intron 1 of 2	2		ENSP00000391489.1	H7BZU6
SIGLEC11	ENST00000426296.1 link	n.176-333G>C		intron_variant	Intron 1 of 2	2		ENSP00000407387.1	H7C2S0

Frequencies

GnomAD3 genomes

AF:

0.000237

AC:

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000323

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000333

AC:

AN:

248910

Hom.:

AF XY:

0.000267

AC XY:

AN XY:

134942

show subpopulations

Gnomad AFR exome

AF:

0.0000621

Gnomad AMR exome

AF:

0.0000869

Gnomad ASJ exome

AF:

0.00428

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000302

Gnomad OTH exome

AF:

0.000328

GnomAD4 exome

AF:

0.000292

AC:

426

AN:

1460370

Hom.:

Cov.:

AF XY:

0.000290

AC XY:

211

AN XY:

726592

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000895

Gnomad4 ASJ exome

AF:

0.00379

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000279

Gnomad4 OTH exome

AF:

0.000199

GnomAD4 genome

AF:

0.000237

AC:

AN:

152188

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000323

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000407

Hom.:

Bravo

AF:

0.000261

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.000296

AC:

EpiCase

AF:

0.000600

EpiControl

AF:

0.000356

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.76

CADD

Benign

0.0020

DANN

Benign

0.44

DEOGEN2

Benign

0.0020

T;.

Eigen

Benign

-2.2

Eigen_PC

Benign

-2.3

FATHMM_MKL

Benign

0.0022

LIST_S2

Benign

0.21

T;T

M_CAP

Benign

0.0022

MetaRNN

Benign

0.0059

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.075

N;.

PrimateAI

Benign

0.39

PROVEAN

Benign

0.24

N;.

REVEL

Benign

0.0090

Sift

Benign

1.0

T;.

Sift4G

Benign

0.54

T;T

Polyphen

0.0

B;B

Vest4

0.14

MVP

0.27

MPC

0.011

ClinPred

0.022

GERP RS

-6.3

Varity_R

0.027

gMVP

0.14

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over