Genetic Variant SIGLEC11:p.Ile671Val (chr19-49950056-T-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_052884.3(SIGLEC11):c.2011A>G(p.Ile671Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000482 in 1,452,708 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/23 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

SIGLEC11
NM_052884.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.604

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIGLEC11	NM_052884.3 link	c.2011A>G	p.Ile671Val	missense_variant	Exon 11 of 11	ENST00000447370.6	NP_443116.2	Q96RL6-1
SIGLEC11	NM_001135163.1 link	c.1723A>G	p.Ile575Val	missense_variant	Exon 10 of 10		NP_001128635.1	Q96RL6-2
SIGLEC11	XM_005258476.4 link	c.2035A>G	p.Ile679Val	missense_variant	Exon 10 of 10		XP_005258533.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIGLEC11	ENST00000447370.6 link	c.2011A>G	p.Ile671Val	missense_variant	Exon 11 of 11	1	NM_052884.3	ENSP00000412361.2		Q96RL6-1
ENSG00000269179	ENST00000451973.1 link	n.*77+1835A>G		intron_variant	Intron 2 of 2	2		ENSP00000391489.1		H7BZU6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000202

AC:

AN:

247526

Hom.:

AF XY:

0.0000299

AC XY:

AN XY:

133894

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000148

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000482

AC:

AN:

1452708

Hom.:

Cov.:

AF XY:

0.00000693

AC XY:

AN XY:

721768

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000159

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 23, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2011A>G (p.I671V) alteration is located in exon 11 (coding exon 11) of the SIGLEC11 gene. This alteration results from a A to G substitution at nucleotide position 2011, causing the isoleucine (I) at amino acid position 671 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.53

CADD

Benign

5.1

DANN

Benign

0.64

DEOGEN2

Benign

0.0016

T;.

Eigen

Benign

-0.74

Eigen_PC

Benign

-0.72

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.59

T;T

M_CAP

Benign

0.0036

MetaRNN

Benign

0.074

T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.3

L;.

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.070

N;.

REVEL

Benign

0.12

Sift

Benign

0.45

T;.

Sift4G

Benign

0.20

T;T

Polyphen

0.019

B;B

Vest4

0.10

MutPred

0.58

Loss of stability (P = 0.0807);.;

MVP

0.36

MPC

0.011

ClinPred

0.066

GERP RS

0.19

Varity_R

0.050

gMVP

0.046

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.41

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.41

Position offset: 1

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over