19-51528229-C-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001245.7(SIGLEC6):​c.1037G>A​(p.Gly346Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000482 in 1,614,152 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0025 ( 2 hom., cov: 31)
Exomes 𝑓: 0.00027 ( 0 hom. )

Consequence

SIGLEC6
NM_001245.7 missense

Scores

19

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.19
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 Benign. Variant got -16 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.008871019).
BP6
Variant 19-51528229-C-T is Benign according to our data. Variant chr19-51528229-C-T is described in ClinVar as [Benign]. Clinvar id is 729001.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SIGLEC6NM_001245.7 linkc.1037G>A p.Gly346Asp 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.1037G>A p.Gly346Asp missense_variant Exon 6 of 8 2 NM_001245.7 ENSP00000401502.2 O43699-1

Frequencies

GnomAD3 genomes
AF:
0.00251
AC:
382
AN:
152192
Hom.:
2
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00847
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00131
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:
0.00335
GnomAD3 exomes
AF:
0.000565
AC:
141
AN:
249560
Hom.:
0
AF XY:
0.000384
AC XY:
52
AN XY:
135390
show subpopulations
Gnomad AFR exome
AF:
0.00756
Gnomad AMR exome
AF:
0.000550
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:
0.0000177
Gnomad OTH exome
AF:
0.000495
GnomAD4 exome
AF:
0.000271
AC:
396
AN:
1461842
Hom.:
0
Cov.:
31
AF XY:
0.000209
AC XY:
152
AN XY:
727226
show subpopulations
Gnomad4 AFR exome
AF:
0.00851
Gnomad4 AMR exome
AF:
0.000514
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:
0.0000405
Gnomad4 OTH exome
AF:
0.000695
GnomAD4 genome
AF:
0.00251
AC:
382
AN:
152310
Hom.:
2
Cov.:
31
AF XY:
0.00251
AC XY:
187
AN XY:
74472
show subpopulations
Gnomad4 AFR
AF:
0.00845
Gnomad4 AMR
AF:
0.00131
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:
0.00332
Alfa
AF:
0.0464
Hom.:
2354
Bravo
AF:
0.00303
ESP6500AA
AF:
0.00786
AC:
31
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.000670
AC:
81

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
-
Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Sep 11, 2018
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.14
BayesDel_addAF
Benign
-0.56
T
BayesDel_noAF
Benign
-0.57
CADD
Benign
0.25
DANN
Benign
0.58
DEOGEN2
Benign
0.0028
.;.;.;T
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.00089
N
LIST_S2
Benign
0.34
T;T;T;T
M_CAP
Benign
0.0034
T
MetaRNN
Benign
0.0089
T;T;T;T
MetaSVM
Benign
-0.92
T
MutationAssessor
Benign
1.7
.;.;.;L
PrimateAI
Benign
0.36
T
PROVEAN
Benign
-1.1
.;N;N;N
REVEL
Benign
0.11
Sift
Benign
0.63
.;T;T;T
Sift4G
Benign
0.63
T;T;T;T
Polyphen
0.99
D;.;.;B
Vest4
0.20
MVP
0.27
MPC
0.20
ClinPred
0.034
T
GERP RS
-5.0
Varity_R
0.047
gMVP
0.20

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: rs182869426; hg19: chr19-52031483; API