Variant 19-51630310-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_003830.4(SIGLEC5):c.26T>C(p.Leu9Pro) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00084 ( 1 hom., cov: 13)

Exomes 𝑓: 0.00081 ( 2 hom. )

Consequence

SIGLEC5
NM_003830.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.06

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010930002).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SIGLEC5	NM_003830.4 linkuse as main transcript	c.26T>C	p.Leu9Pro	missense_variant	1/9	ENST00000683636.1	NP_003821.1
SIGLEC5	NM_001384708.1 linkuse as main transcript	c.26T>C	p.Leu9Pro	missense_variant	1/8		NP_001371637.1
SIGLEC5	NM_001384709.1 linkuse as main transcript	c.26T>C	p.Leu9Pro	missense_variant	1/8		NP_001371638.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SIGLEC5	ENST00000683636.1 linkuse as main transcript	c.26T>C	p.Leu9Pro	missense_variant	1/9		NM_003830.4	ENSP00000507738	P1

Frequencies

GnomAD3 genomes

AF:

0.000839

AC:

AN:

98964

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000127

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000591

Gnomad ASJ

AF:

0.00368

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00120

Gnomad FIN

AF:

0.000174

Gnomad MID

AF:

0.0147

Gnomad NFE

AF:

0.00111

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000819

AC:

AN:

50036

Hom.:

AF XY:

0.000950

AC XY:

AN XY:

25250

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000839

Gnomad ASJ exome

AF:

0.00236

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000474

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00132

Gnomad OTH exome

AF:

0.00120

GnomAD4 exome

AF:

0.000814

AC:

570

AN:

700170

Hom.:

Cov.:

AF XY:

0.000842

AC XY:

298

AN XY:

353886

show subpopulations

Gnomad4 AFR exome

AF:

0.000306

Gnomad4 AMR exome

AF:

0.000597

Gnomad4 ASJ exome

AF:

0.00232

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000477

Gnomad4 FIN exome

AF:

0.0000343

Gnomad4 NFE exome

AF:

0.000831

Gnomad4 OTH exome

AF:

0.00131

GnomAD4 genome

AF:

0.000838

AC:

AN:

99040

Hom.:

Cov.:

AF XY:

0.000846

AC XY:

AN XY:

46092

show subpopulations

Gnomad4 AFR

AF:

0.000127

Gnomad4 AMR

AF:

0.000590

Gnomad4 ASJ

AF:

0.00368

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00121

Gnomad4 FIN

AF:

0.000174

Gnomad4 NFE

AF:

0.00111

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000785

Hom.:

ExAC

AF:

0.0000746

AC:

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

Jan 04, 2024

The c.26T>C (p.L9P) alteration is located in exon 1 (coding exon 1) of the SIGLEC5 gene. This alteration results from a T to C substitution at nucleotide position 26, causing the leucine (L) at amino acid position 9 to be replaced by a proline (P). 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

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Uncertain

-0.040

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.23

Eigen

Uncertain

0.50

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.31

MetaRNN

Benign

0.011

MetaSVM

Benign

-0.37

MutationAssessor

Pathogenic

3.3

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.76

Sift4G

Uncertain

0.0020

Polyphen

1.0

Vest4

0.75

MutPred

0.79

Gain of loop (P = 0.024);

MVP

0.79

ClinPred

0.18

GERP RS

3.0

Varity_R

0.75

gMVP

0.32

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