chr20-3691442-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_023068.4(SIGLEC1):​c.4489G>A​(p.Ala1497Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,613,288 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

SIGLEC1
NM_023068.4 missense

Scores

19

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -4.71
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.018843025).
BP6
Variant 20-3691442-C-T is Benign according to our data. Variant chr20-3691442-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2510767.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SIGLEC1NM_023068.4 linkuse as main transcriptc.4489G>A p.Ala1497Thr missense_variant 18/22 ENST00000344754.6
SIGLEC1NM_001367089.1 linkuse as main transcriptc.4489G>A p.Ala1497Thr missense_variant 17/20

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SIGLEC1ENST00000344754.6 linkuse as main transcriptc.4489G>A p.Ala1497Thr missense_variant 18/221 NM_023068.4 P2Q9BZZ2-1
SIGLEC1ENST00000707083.1 linkuse as main transcriptc.4489G>A p.Ala1497Thr missense_variant 17/20 A2
SIGLEC1ENST00000419548.4 linkuse as main transcriptc.931G>A p.Ala311Thr missense_variant 4/52

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152238
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000723
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:
0.0000120
AC:
3
AN:
250568
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135712
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000289
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:
0.0000177
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000110
AC:
16
AN:
1460932
Hom.:
0
Cov.:
33
AF XY:
0.0000110
AC XY:
8
AN XY:
726780
show subpopulations
Gnomad4 AFR exome
AF:
0.0000597
Gnomad4 AMR exome
AF:
0.0000224
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:
0.0000117
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152356
Hom.:
0
Cov.:
33
AF XY:
0.0000268
AC XY:
2
AN XY:
74502
show subpopulations
Gnomad4 AFR
AF:
0.0000721
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
Bravo
AF:
0.00000378
ExAC
AF:
0.00000824
AC:
1
EpiCase
AF:
0.000109
EpiControl
AF:
0.00

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsMay 08, 2023This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.072
BayesDel_addAF
Benign
-0.39
T
BayesDel_noAF
Benign
-0.62
CADD
Benign
0.016
DANN
Benign
0.54
DEOGEN2
Benign
0.042
T
Eigen
Benign
-1.8
Eigen_PC
Benign
-2.0
FATHMM_MKL
Benign
0.0053
N
LIST_S2
Benign
0.55
T
M_CAP
Benign
0.0017
T
MetaRNN
Benign
0.019
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-1.1
N
MutationTaster
Benign
1.0
N;N
PrimateAI
Benign
0.32
T
PROVEAN
Benign
0.72
N
REVEL
Benign
0.036
Sift
Benign
0.76
T
Sift4G
Benign
1.0
T
Polyphen
0.0040
B
Vest4
0.037
MutPred
0.28
Gain of catalytic residue at A1497 (P = 0.0452);
MVP
0.048
MPC
0.11
ClinPred
0.081
T
GERP RS
-11
Varity_R
0.029
gMVP
0.13

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.

Other links and lift over

dbSNP: rs780246801; hg19: chr20-3672089; COSMIC: COSV52464983; API