Variant 19-51630168-A-G 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.86T>C(p.Val29Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00039 ( 0 hom., cov: 6)

Exomes 𝑓: 0.000045 ( 0 hom. )

Consequence

SIGLEC5
NM_003830.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.60

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=0.10267022).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SIGLEC5	NM_003830.4 linkuse as main transcript	c.86T>C	p.Val29Ala	missense_variant	2/9	ENST00000683636.1	NP_003821.1
SIGLEC5	NM_001384708.1 linkuse as main transcript	c.86T>C	p.Val29Ala	missense_variant	2/8		NP_001371637.1
SIGLEC5	NM_001384709.1 linkuse as main transcript	c.86T>C	p.Val29Ala	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.86T>C	p.Val29Ala	missense_variant	2/9		NM_003830.4	ENSP00000507738	P1

Frequencies

GnomAD3 genomes

AF:

0.000389

AC:

AN:

46326

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00157

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000211

AC:

AN:

56784

Hom.:

AF XY:

0.000176

AC XY:

AN XY:

28456

show subpopulations

Gnomad AFR exome

AF:

0.00221

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000450

AC:

AN:

510634

Hom.:

Cov.:

AF XY:

0.0000376

AC XY:

AN XY:

266284

show subpopulations

Gnomad4 AFR exome

AF:

0.00136

Gnomad4 AMR exome

AF:

0.000103

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:

0.00000308

Gnomad4 OTH exome

AF:

0.0000357

GnomAD4 genome

AF:

0.000388

AC:

AN:

46334

Hom.:

Cov.:

AF XY:

0.000249

AC XY:

AN XY:

20090

show subpopulations

Gnomad4 AFR

AF:

0.00156

Gnomad4 AMR

AF:

0.00

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:

0.0000843

Hom.:

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

Aug 09, 2021

The c.86T>C (p.V29A) alteration is located in exon 2 (coding exon 2) of the SIGLEC5 gene. This alteration results from a T to C substitution at nucleotide position 86, causing the valine (V) at amino acid position 29 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

0.26

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.17

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.15

T;.

Eigen

Uncertain

0.40

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Benign

0.42

LIST_S2

Benign

0.63

T;.

M_CAP

Uncertain

0.13

MetaRNN

Benign

0.10

T;T

MetaSVM

Uncertain

0.11

MutationAssessor

Pathogenic

3.4

M;.

MutationTaster

Benign

1.0

D;N

PrimateAI

Uncertain

0.65

PROVEAN

Uncertain

-3.8

.;D

REVEL

Uncertain

0.52

Sift

Uncertain

0.0050

.;D

Sift4G

Uncertain

0.0030

D;D

Polyphen

1.0

D;.

Vest4

0.30

MutPred

0.67

Gain of ubiquitination at K27 (P = 0.0523);Gain of ubiquitination at K27 (P = 0.0523);

MVP

0.83

ClinPred

0.28

GERP RS

4.2

Varity_R

0.46

gMVP

0.21

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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