Genetic Variant SIGLEC11:p.Ser620Arg (chr19-49950207-G-C) – 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.1860C>G(p.Ser620Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000501 in 1,597,002 control chromosomes in the GnomAD database, including 1 homozygotes. 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: 𝑓 0.00024 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000030 ( 1 hom. )

Consequence

SIGLEC11
NM_052884.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.237

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=0.030989677).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIGLEC11	NM_052884.3 link	c.1860C>G	p.Ser620Arg	missense_variant	Exon 11 of 11	ENST00000447370.6	NP_443116.2	Q96RL6-1
SIGLEC11	NM_001135163.1 link	c.1572C>G	p.Ser524Arg	missense_variant	Exon 10 of 10		NP_001128635.1	Q96RL6-2
SIGLEC11	XM_005258476.4 link	c.1884C>G	p.Ser628Arg	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.1860C>G	p.Ser620Arg	missense_variant	Exon 11 of 11	1	NM_052884.3	ENSP00000412361.2		Q96RL6-1
ENSG00000269179	ENST00000451973.1 link	n.*77+1684C>G		intron_variant	Intron 2 of 2	2		ENSP00000391489.1		H7BZU6

Frequencies

GnomAD3 genomes

AF:

0.000237

AC:

AN:

152132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000845

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000778

AC:

AN:

231308

Hom.:

AF XY:

0.0000475

AC XY:

AN XY:

126238

show subpopulations

Gnomad AFR exome

AF:

0.00113

Gnomad AMR exome

AF:

0.0000310

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:

0.0000305

AC:

AN:

1444870

Hom.:

Cov.:

AF XY:

0.0000223

AC XY:

AN XY:

718518

show subpopulations

Gnomad4 AFR exome

AF:

0.00108

Gnomad4 AMR exome

AF:

0.0000460

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:

0.000100

GnomAD4 genome

AF:

0.000237

AC:

AN:

152132

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.000845

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000504

Hom.:

Bravo

AF:

0.000310

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 07, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1860C>G (p.S620R) alteration is located in exon 11 (coding exon 11) of the SIGLEC11 gene. This alteration results from a C to G substitution at nucleotide position 1860, causing the serine (S) at amino acid position 620 to be replaced by an arginine (R). 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

0.18

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.52

CADD

Benign

3.7

DANN

Uncertain

0.98

DEOGEN2

Benign

0.024

T;.

Eigen

Benign

-0.63

Eigen_PC

Benign

-0.85

FATHMM_MKL

Benign

0.017

LIST_S2

Benign

0.50

T;T

M_CAP

Benign

0.0051

MetaRNN

Benign

0.031

T;T

MetaSVM

Benign

-0.88

MutationAssessor

Benign

2.0

M;.

PrimateAI

Benign

0.28

PROVEAN

Benign

-2.3

N;.

REVEL

Benign

0.13

Sift

Benign

0.34

T;.

Sift4G

Benign

0.072

T;T

Polyphen

0.0010

B;D

Vest4

0.21

MutPred

0.15

Loss of glycosylation at S620 (P = 0.0233);.;

MVP

0.64

MPC

0.011

ClinPred

0.071

GERP RS

-0.94

Varity_R

0.20

gMVP

0.10

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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