19-51528241-C-T

Variant summary

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

The NM_001245.7(SIGLEC6):​c.1025G>A​(p.Gly342Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,718 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G342V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SIGLEC6
NM_001245.7 missense

Scores

1
18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.302
Variant links:
Genes affected
SIGLEC6 (HGNC:10875): (sialic acid binding Ig like lectin 6) This gene encodes a member of the SIGLEC (sialic acid binding immunoglobulin-like lectin) family of proteins. The encoded transmembrane receptor binds sialyl-TN glycans and leptin. Placental expression of the encoded protein is upregulated in preeclampsia. [provided by RefSeq, Jul 2016]

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=0.103345096).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SIGLEC6NM_001245.7 linkc.1025G>A p.Gly342Asp missense_variant Exon 6 of 8 ENST00000425629.8 NP_001236.4 O43699-1A0A024R4K4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SIGLEC6ENST00000425629.8 linkc.1025G>A p.Gly342Asp missense_variant Exon 6 of 8 2 NM_001245.7 ENSP00000401502.2 O43699-1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD3 exomes
AF:
0.00000401
AC:
1
AN:
249510
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135368
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000290
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461718
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
727184
show subpopulations
Gnomad4 AFR exome
AF:
0.00
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.096
BayesDel_addAF
Benign
-0.20
T
BayesDel_noAF
Benign
-0.44
CADD
Benign
5.4
DANN
Benign
0.22
DEOGEN2
Benign
0.0039
.;.;.;T
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.2
FATHMM_MKL
Benign
0.015
N
LIST_S2
Benign
0.41
T;T;T;T
M_CAP
Benign
0.0047
T
MetaRNN
Benign
0.10
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.55
.;.;.;N
PrimateAI
Benign
0.32
T
PROVEAN
Pathogenic
-5.4
D;N;N;N
REVEL
Benign
0.15
Sift
Benign
0.038
D;T;T;D
Sift4G
Benign
0.11
T;T;T;T
Polyphen
0.57
P;.;.;B
Vest4
0.19
MutPred
0.45
.;.;.;Loss of methylation at R343 (P = 0.0537);
MVP
0.095
MPC
0.46
ClinPred
0.58
D
GERP RS
0.52
Varity_R
0.073
gMVP
0.089

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: rs1323409813; hg19: chr19-52031495; API