Genetic Variant SIGLEC11:p.Val537Ala (chr19-49958324-A-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.1610T>C(p.Val537Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000171 in 1,461,856 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 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: 0.000017 ( 0 hom. )

Consequence

SIGLEC11
NM_052884.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.435

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=0.029201).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIGLEC11	NM_052884.3 link	c.1610T>C	p.Val537Ala	missense_variant	Exon 8 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.1610T>C	p.Val537Ala	missense_variant	Exon 8 of 11	1	NM_052884.3	ENSP00000412361.2	Q96RL6-1
SIGLEC11	ENST00000426971.2 link	c.1363+319T>C		intron_variant	Intron 7 of 9	1		ENSP00000398891.2	Q96RL6-2
ENSG00000269179	ENST00000451973.1 link	n.68T>C		non_coding_transcript_exon_variant	Exon 1 of 3	2		ENSP00000391489.1	H7BZU6
SIGLEC11	ENST00000426296.1 link	n.134T>C		non_coding_transcript_exon_variant	Exon 1 of 3	2		ENSP00000407387.1	H7C2S0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000520

AC:

AN:

249934

Hom.:

AF XY:

0.0000739

AC XY:

AN XY:

135356

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:

0.000425

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000171

AC:

AN:

1461856

Hom.:

Cov.:

AF XY:

0.0000261

AC XY:

AN XY:

727230

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:

0.000278

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000741

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 22, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1610T>C (p.V537A) alteration is located in exon 8 (coding exon 8) of the SIGLEC11 gene. This alteration results from a T to C substitution at nucleotide position 1610, causing the valine (V) at amino acid position 537 to be replaced by an alanine (A). 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

0.11

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.65

CADD

Benign

0.11

DANN

Benign

0.35

DEOGEN2

Benign

0.0046

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0026

LIST_S2

Benign

0.051

M_CAP

Benign

0.0014

MetaRNN

Benign

0.029

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.64

PROVEAN

Benign

-1.4

REVEL

Benign

0.020

Sift

Benign

0.42

Sift4G

Benign

0.80

Polyphen

0.078

Vest4

0.28

MutPred

0.39

Gain of disorder (P = 0.0345);

MVP

0.040

MPC

0.013

ClinPred

0.051

GERP RS

-3.7

Varity_R

0.035

gMVP

0.11

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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