chr19-51520177-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.1267G>A​(p.Glu423Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

SIGLEC6
NM_001245.7 missense

Scores

1
4
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.29
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]

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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=0.21054009).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SIGLEC6NM_001245.7 linkc.1267G>A p.Glu423Lys missense_variant Exon 8 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.1267G>A p.Glu423Lys missense_variant Exon 8 of 8 2 NM_001245.7 ENSP00000401502.2 O43699-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 30, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1267G>A (p.E423K) alteration is located in exon 8 (coding exon 8) of the SIGLEC6 gene. This alteration results from a G to A substitution at nucleotide position 1267, causing the glutamic acid (E) at amino acid position 423 to be replaced by a lysine (K). 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
0.13
BayesDel_addAF
Benign
-0.19
T
BayesDel_noAF
Benign
-0.51
CADD
Benign
18
DANN
Uncertain
1.0
DEOGEN2
Benign
0.026
.;.;T
Eigen
Benign
-0.010
Eigen_PC
Benign
-0.30
FATHMM_MKL
Benign
0.033
N
LIST_S2
Benign
0.82
T;T;D
M_CAP
Benign
0.0060
T
MetaRNN
Benign
0.21
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Pathogenic
2.9
.;.;M
PrimateAI
Benign
0.42
T
PROVEAN
Uncertain
-3.1
.;D;D
REVEL
Benign
0.069
Sift
Uncertain
0.0030
.;D;D
Sift4G
Uncertain
0.0030
D;D;D
Polyphen
1.0
D;.;D
Vest4
0.21
MutPred
0.45
.;.;Gain of ubiquitination at E423 (P = 0.0075);
MVP
0.17
MPC
0.17
ClinPred
0.86
D
GERP RS
2.6
Varity_R
0.23
gMVP
0.44

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-52023431; API