Variant 19-51630108-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_003830.4(SIGLEC5):c.146C>G(p.Ser49Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000087 ( 0 hom., cov: 5)

Exomes 𝑓: 0.000019 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SIGLEC5
NM_003830.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -3.38

Variant links:

Genes affected

SIGLEC5 (HGNC:10874): (sialic acid binding Ig like lectin 5) This gene encodes a member of the sialic acid-binding immunoglobulin-like lectin (Siglec) 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. The encoded protein is a member of the CD33-related subset of Siglecs and inhibits the activation of several cell types including monocytes, macrophages and neutrophils. Binding of group B Streptococcus (GBS) to the encoded protein plays a role in GBS immune evasion. [provided by RefSeq, Feb 2012]

SIGLEC5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0966571).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SIGLEC5	NM_003830.4 linkuse as main transcript	c.146C>G	p.Ser49Cys	missense_variant	2/9	ENST00000683636.1	NP_003821.1
SIGLEC5	NM_001384708.1 linkuse as main transcript	c.146C>G	p.Ser49Cys	missense_variant	2/8		NP_001371637.1
SIGLEC5	NM_001384709.1 linkuse as main transcript	c.146C>G	p.Ser49Cys	missense_variant	2/8		NP_001371638.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SIGLEC5	ENST00000683636.1 linkuse as main transcript	c.146C>G	p.Ser49Cys	missense_variant	2/9		NM_003830.4	ENSP00000507738	P1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

34456

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00187

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:

0.0000983

AC:

AN:

71200

Hom.:

AF XY:

0.000137

AC XY:

AN XY:

36392

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000651

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000443

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000189

AC:

AN:

528842

Hom.:

Cov.:

AF XY:

0.0000254

AC XY:

AN XY:

275774

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000283

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000348

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000871

AC:

AN:

34456

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

15150

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00187

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 28, 2023

The c.146C>G (p.S49C) alteration is located in exon 2 (coding exon 2) of the SIGLEC5 gene. This alteration results from a C to G substitution at nucleotide position 146, causing the serine (S) at amino acid position 49 to be replaced by a cysteine (C). 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

0.32

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

0.46

DANN

Benign

0.88

DEOGEN2

Benign

0.050

T;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0054

LIST_S2

Benign

0.023

T;.

M_CAP

Benign

0.019

MetaRNN

Benign

0.097

T;T

MetaSVM

Benign

-0.50

MutationAssessor

Uncertain

2.5

M;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.36

PROVEAN

Uncertain

-2.6

.;D

REVEL

Benign

0.29

Sift

Benign

0.15

.;T

Sift4G

Uncertain

0.023

D;D

Polyphen

0.99

D;.

Vest4

0.19

MutPred

0.72

Gain of catalytic residue at W50 (P = 0.013);Gain of catalytic residue at W50 (P = 0.013);

MVP

0.33

ClinPred

0.25

GERP RS

-8.5

Varity_R

0.22

gMVP

0.090

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