Variant chr20-3690171-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_023068.4(SIGLEC1):c.4685C>T(p.Ala1562Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000279 in 1,433,184 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000028 ( 1 hom. )

Consequence

SIGLEC1
NM_023068.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.93

Variant links:

Genes affected

SIGLEC1 (HGNC:11127): (sialic acid binding Ig like lectin 1) This gene encodes a member of the immunoglobulin superfamily. The encoded protein is a lectin-like adhesion molecule that binds glycoconjugate ligands on cell surfaces in a sialic acid-dependent manner. It is a type I transmembrane protein expressed only by a subpopulation of macrophages and is involved in mediating cell-cell interactions. The protein plays an important role in multiple human diseases and bacterial and viral infections has been shown to enhance SARS-CoV-2 infection. [provided by RefSeq, Dec 2021]

SIGLEC1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.81

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SIGLEC1	NM_023068.4 linkuse as main transcript	c.4685C>T	p.Ala1562Val	missense_variant	19/22	ENST00000344754.6
SIGLEC1	NM_001367089.1 linkuse as main transcript	c.4685C>T	p.Ala1562Val	missense_variant	18/20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SIGLEC1	ENST00000344754.6 linkuse as main transcript	c.4685C>T	p.Ala1562Val	missense_variant	19/22	1	NM_023068.4	P2	Q9BZZ2-1
SIGLEC1	ENST00000707083.1 linkuse as main transcript	c.4685C>T	p.Ala1562Val	missense_variant	18/20			A2
SIGLEC1	ENST00000419548.4 linkuse as main transcript	c.1127C>T	p.Ala376Val	missense_variant	5/5	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000202

AC:

AN:

198002

Hom.:

AF XY:

0.0000280

AC XY:

AN XY:

107286

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:

0.00

Gnomad FIN exome

AF:

0.000227

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000279

AC:

AN:

1433184

Hom.:

Cov.:

AF XY:

0.00000422

AC XY:

AN XY:

710384

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:

0.00

Gnomad4 FIN exome

AF:

0.0000795

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Jun 18, 2021

The c.4685C>T (p.A1562V) alteration is located in exon 18 (coding exon 18) of the SIGLEC1 gene. This alteration results from a C to T substitution at nucleotide position 4685, causing the alanine (A) at amino acid position 1562 to be replaced by a valine (V). 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

Uncertain

0.48

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Uncertain

-0.080

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.087

Eigen

Pathogenic

0.76

Eigen_PC

Pathogenic

0.70

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.81

M_CAP

Benign

0.078

MetaRNN

Pathogenic

0.81

MetaSVM

Uncertain

0.36

MutationAssessor

Pathogenic

3.4

MutationTaster

Benign

0.58

N;N

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.73

REVEL

Uncertain

0.41

Sift

Benign

0.13

Sift4G

Uncertain

0.012

Polyphen

1.0

Vest4

0.43

MutPred

0.80

Gain of sheet (P = 0.0827);

MVP

0.83

MPC

0.53

ClinPred

0.69

GERP RS

5.3

Varity_R

0.11

gMVP

0.55

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