Variant 19-51530858-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001245.7(SIGLEC6):c.529C>T(p.Pro177Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00112 in 1,613,944 control chromosomes in the GnomAD database, including 3 homozygotes. 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: 𝑓 0.00081 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 3 hom. )

Consequence

SIGLEC6
NM_001245.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.486

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.02895078).

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SIGLEC6	NM_001245.7 linkuse as main transcript	c.529C>T	p.Pro177Ser	missense_variant	3/8	ENST00000425629.8	NP_001236.4	O43699-1A0A024R4K4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SIGLEC6	ENST00000425629.8 linkuse as main transcript	c.529C>T	p.Pro177Ser	missense_variant	3/8	2	NM_001245.7	ENSP00000401502.2		O43699-1

Frequencies

GnomAD3 genomes

AF:

0.000808

AC:

123

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00160

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000741

AC:

186

AN:

251056

Hom.:

AF XY:

0.000722

AC XY:

AN XY:

135716

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.0000868

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000327

Gnomad NFE exome

AF:

0.00149

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.00115

AC:

1677

AN:

1461658

Hom.:

Cov.:

AF XY:

0.00112

AC XY:

815

AN XY:

727130

show subpopulations

Gnomad4 AFR exome

AF:

0.000358

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000263

Gnomad4 NFE exome

AF:

0.00145

Gnomad4 OTH exome

AF:

0.000596

GnomAD4 genome

AF:

0.000808

AC:

123

AN:

152286

Hom.:

Cov.:

AF XY:

0.000645

AC XY:

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.000193

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.00160

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000898

Hom.:

Bravo

AF:

0.000740

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00311

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00116

AC:

ExAC

AF:

0.000717

AC:

EpiCase

AF:

0.00104

EpiControl

AF:

0.00101

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 23, 2021

The c.529C>T (p.P177S) alteration is located in exon 3 (coding exon 3) of the SIGLEC6 gene. This alteration results from a C to T substitution at nucleotide position 529, causing the proline (P) at amino acid position 177 to be replaced by a serine (S). 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

0.15

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.056

.;.;.;.;T;.

Eigen

Benign

-0.30

Eigen_PC

Benign

-0.50

FATHMM_MKL

Benign

0.017

LIST_S2

Benign

0.77

T;T;T;T;T;T

M_CAP

Benign

0.0080

MetaRNN

Benign

0.029

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.4

M;M;.;M;M;.

PrimateAI

Benign

0.34

PROVEAN

Pathogenic

-6.7

.;D;D;D;D;.

REVEL

Benign

0.069

Sift

Uncertain

0.0040

.;D;D;D;D;.

Sift4G

Uncertain

0.041

D;T;D;T;D;T

Polyphen

0.83

P;.;.;D;P;P

Vest4

0.23

MVP

0.081

MPC

0.52

ClinPred

0.10

GERP RS

2.3

Varity_R

0.18

gMVP

0.46

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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