Genetic Variant SIGLEC11:p.Ala595Thr (chr19-49951938-C-T) – 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.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. 15/21 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

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=0.06664166).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIGLEC11	NM_052884.3 link	c.1783G>A	p.Ala595Thr	missense_variant	Exon 10 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.1783G>A	p.Ala595Thr	missense_variant	Exon 10 of 11	1	NM_052884.3	ENSP00000412361.2	Q96RL6-1
ENSG00000269179	ENST00000451973.1 link	n.*30G>A		non_coding_transcript_exon_variant	Exon 2 of 3	2		ENSP00000391489.1	H7BZU6
ENSG00000269179	ENST00000451973.1 link	n.*30G>A		3_prime_UTR_variant	Exon 2 of 3	2		ENSP00000391489.1	H7BZU6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000405

AC:

AN:

247116

Hom.:

AF XY:

0.00000748

AC XY:

AN XY:

133690

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 SAS 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

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.0000567

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000189

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

Oct 08, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1783G>A (p.A595T) alteration is located in exon 10 (coding exon 10) of the SIGLEC11 gene. This alteration results from a G to A substitution at nucleotide position 1783, causing the alanine (A) at amino acid position 595 to be replaced by a threonine (T). 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

0.084

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.62

CADD

Benign

5.1

DANN

Uncertain

0.99

DEOGEN2

Benign

0.00093

T;.

Eigen

Benign

-0.95

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.027

LIST_S2

Benign

0.54

T;T

M_CAP

Benign

0.0025

MetaRNN

Benign

0.067

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.94

L;.

PrimateAI

Benign

0.28

PROVEAN

Benign

0.37

N;.

REVEL

Benign

0.12

Sift

Benign

0.67

T;.

Sift4G

Benign

0.34

T;T

Polyphen

0.26

B;P

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

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

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