Genetic Variant SIGLEC6:p.Gly346Asp (chr19-51528229-C-T) – ACMG Classification: Benign (-16 pts)

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

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]

SIGLEC6 links:

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
SIGLEC6	NM_001245.7 link	c.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
SIGLEC6	ENST00000425629.8 link	c.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.:

Cov.:

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.:

AF XY:

0.000384

AC XY:

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.:

Cov.:

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.:

Cov.:

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:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000670

AC:

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

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

LIST_S2

Benign

0.34

T;T;T;T

M_CAP

Benign

0.0034

MetaRNN

Benign

0.0089

T;T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.7

.;.;.;L

PrimateAI

Benign

0.36

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

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over