chr20-3691580-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_023068.4(SIGLEC1):​c.4351C>T​(p.Pro1451Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000329 in 1,612,492 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000034 ( 0 hom. )

Consequence

SIGLEC1
NM_023068.4 missense

Scores

4
6
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.97
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 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SIGLEC1NM_023068.4 linkuse as main transcriptc.4351C>T p.Pro1451Ser missense_variant 18/22 ENST00000344754.6
SIGLEC1NM_001367089.1 linkuse as main transcriptc.4351C>T p.Pro1451Ser missense_variant 17/20

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SIGLEC1ENST00000344754.6 linkuse as main transcriptc.4351C>T p.Pro1451Ser missense_variant 18/221 NM_023068.4 P2Q9BZZ2-1
SIGLEC1ENST00000707083.1 linkuse as main transcriptc.4351C>T p.Pro1451Ser missense_variant 17/20 A2
SIGLEC1ENST00000419548.4 linkuse as main transcriptc.793C>T p.Pro265Ser missense_variant 4/52

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152282
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.0000588
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000283
AC:
7
AN:
247476
Hom.:
0
AF XY:
0.0000297
AC XY:
4
AN XY:
134486
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:
0.00
Gnomad NFE exome
AF:
0.0000631
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000336
AC:
49
AN:
1460210
Hom.:
0
Cov.:
33
AF XY:
0.0000385
AC XY:
28
AN XY:
726386
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:
0.00
Gnomad4 NFE exome
AF:
0.0000432
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152282
Hom.:
0
Cov.:
33
AF XY:
0.0000269
AC XY:
2
AN XY:
74404
show subpopulations
Gnomad4 AFR
AF:
0.00
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:
0.0000588
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000566
Hom.:
0
Bravo
AF:
0.0000113
ExAC
AF:
0.0000495
AC:
6

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 GeneticsOct 26, 2022The c.4351C>T (p.P1451S) alteration is located in exon 17 (coding exon 17) of the SIGLEC1 gene. This alteration results from a C to T substitution at nucleotide position 4351, causing the proline (P) at amino acid position 1451 to be replaced by a serine (S). 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
0.30
BayesDel_addAF
Benign
-0.17
T
BayesDel_noAF
Benign
-0.29
CADD
Uncertain
24
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.22
T
Eigen
Uncertain
0.56
Eigen_PC
Uncertain
0.50
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Benign
0.81
T
M_CAP
Benign
0.016
T
MetaRNN
Uncertain
0.72
D
MetaSVM
Benign
-0.91
T
MutationAssessor
Pathogenic
3.1
M
MutationTaster
Benign
0.98
D;D
PrimateAI
Benign
0.39
T
PROVEAN
Uncertain
-2.4
N
REVEL
Uncertain
0.31
Sift
Uncertain
0.017
D
Sift4G
Pathogenic
0.0
D
Polyphen
1.0
D
Vest4
0.52
MVP
0.47
MPC
0.54
ClinPred
0.93
D
GERP RS
5.3
Varity_R
0.11
gMVP
0.86

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: rs750416976; hg19: chr20-3672227; COSMIC: COSV99171454; API