chr20-3690126-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_023068.4(SIGLEC1):​c.4730A>T​(p.Gln1577Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000211 in 1,608,582 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

SIGLEC1
NM_023068.4 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.364
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.13174301).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SIGLEC1NM_023068.4 linkuse as main transcriptc.4730A>T p.Gln1577Leu missense_variant 19/22 ENST00000344754.6
SIGLEC1NM_001367089.1 linkuse as main transcriptc.4730A>T p.Gln1577Leu missense_variant 18/20

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SIGLEC1ENST00000344754.6 linkuse as main transcriptc.4730A>T p.Gln1577Leu missense_variant 19/221 NM_023068.4 P2Q9BZZ2-1
SIGLEC1ENST00000707083.1 linkuse as main transcriptc.4730A>T p.Gln1577Leu missense_variant 18/20 A2
SIGLEC1ENST00000419548.4 linkuse as main transcriptc.1172A>T p.Gln391Leu missense_variant 5/52

Frequencies

GnomAD3 genomes
AF:
0.0000854
AC:
13
AN:
152184
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000785
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000126
AC:
3
AN:
238074
Hom.:
0
AF XY:
0.00000772
AC XY:
1
AN XY:
129450
show subpopulations
Gnomad AFR exome
AF:
0.0000674
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:
0.0000187
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000144
AC:
21
AN:
1456280
Hom.:
0
Cov.:
33
AF XY:
0.0000166
AC XY:
12
AN XY:
723998
show subpopulations
Gnomad4 AFR exome
AF:
0.000150
Gnomad4 AMR exome
AF:
0.000113
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:
0.00000721
Gnomad4 OTH exome
AF:
0.0000333
GnomAD4 genome
AF:
0.0000854
AC:
13
AN:
152302
Hom.:
0
Cov.:
33
AF XY:
0.000107
AC XY:
8
AN XY:
74470
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000784
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.000193
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000330
AC:
4

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 submitterclinical testingAmbry GeneticsJun 22, 2023The c.4730A>T (p.Q1577L) alteration is located in exon 18 (coding exon 18) of the SIGLEC1 gene. This alteration results from a A to T substitution at nucleotide position 4730, causing the glutamine (Q) at amino acid position 1577 to be replaced by a leucine (L). 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
0.093
BayesDel_addAF
Benign
-0.26
T
BayesDel_noAF
Benign
-0.43
CADD
Benign
19
DANN
Uncertain
0.99
DEOGEN2
Benign
0.21
T
Eigen
Benign
-0.12
Eigen_PC
Benign
-0.19
FATHMM_MKL
Benign
0.050
N
LIST_S2
Benign
0.68
T
M_CAP
Benign
0.0053
T
MetaRNN
Benign
0.13
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.1
M
MutationTaster
Benign
1.0
N;N
PrimateAI
Benign
0.31
T
PROVEAN
Benign
-2.1
N
REVEL
Benign
0.13
Sift
Benign
0.13
T
Sift4G
Uncertain
0.015
D
Polyphen
0.98
D
Vest4
0.39
MVP
0.45
MPC
0.13
ClinPred
0.63
D
GERP RS
2.6
Varity_R
0.11
gMVP
0.38

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: rs371324716; hg19: chr20-3670773; API