19-51528241-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001245.7(SIGLEC6):​c.1025G>C​(p.Gly342Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 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 š‘“: 6.8e-7 ( 0 hom. )

Consequence

SIGLEC6
NM_001245.7 missense

Scores

1
1
17

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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.05591768).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SIGLEC6NM_001245.7 linkc.1025G>C p.Gly342Ala 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>C p.Gly342Ala missense_variant Exon 6 of 8 2 NM_001245.7 ENSP00000401502.2 O43699-1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461718
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
727184
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
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:
0.00
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
0.086
BayesDel_addAF
Benign
-0.21
T
BayesDel_noAF
Benign
-0.53
CADD
Benign
0.66
DANN
Benign
0.12
DEOGEN2
Benign
0.00055
.;.;.;T
Eigen
Benign
-1.4
Eigen_PC
Benign
-1.5
FATHMM_MKL
Benign
0.00033
N
LIST_S2
Benign
0.47
T;T;T;T
M_CAP
Benign
0.0033
T
MetaRNN
Benign
0.056
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-0.55
.;.;.;N
PrimateAI
Benign
0.30
T
PROVEAN
Pathogenic
-4.4
D;N;N;N
REVEL
Benign
0.062
Sift
Uncertain
0.0040
D;T;T;T
Sift4G
Benign
0.29
T;T;T;T
Polyphen
0.0090
B;.;.;P
Vest4
0.14
MutPred
0.36
.;.;.;Loss of methylation at K339 (P = 0.0882);
MVP
0.067
MPC
0.20
ClinPred
0.58
D
GERP RS
0.52
Varity_R
0.041
gMVP
0.081

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: chr19-52031495; API