Variant 19-51531183-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001245.7(SIGLEC6):c.404C>T(p.Ser135Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000986 in 1,596,410 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00071 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0010 ( 1 hom. )

Consequence

SIGLEC6
NM_001245.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.628

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 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=0.017716557).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SIGLEC6	NM_001245.7 linkuse as main transcript	c.404C>T	p.Ser135Phe	missense_variant	2/8	ENST00000425629.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SIGLEC6	ENST00000425629.8 linkuse as main transcript	c.404C>T	p.Ser135Phe	missense_variant	2/8	2	NM_001245.7	P2	O43699-1

Frequencies

GnomAD3 genomes

AF:

0.000710

AC:

108

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000410

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00131

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000558

AC:

132

AN:

236542

Hom.:

AF XY:

0.000494

AC XY:

AN XY:

127470

show subpopulations

Gnomad AFR exome

AF:

0.000324

Gnomad AMR exome

AF:

0.0000888

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000488

Gnomad NFE exome

AF:

0.00111

Gnomad OTH exome

AF:

0.000698

GnomAD4 exome

AF:

0.00102

AC:

1466

AN:

1444088

Hom.:

Cov.:

AF XY:

0.000986

AC XY:

706

AN XY:

716288

show subpopulations

Gnomad4 AFR exome

AF:

0.000271

Gnomad4 AMR exome

AF:

0.0000455

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000120

Gnomad4 FIN exome

AF:

0.000114

Gnomad4 NFE exome

AF:

0.00129

Gnomad4 OTH exome

AF:

0.000436

GnomAD4 genome

AF:

0.000709

AC:

108

AN:

152322

Hom.:

Cov.:

AF XY:

0.000564

AC XY:

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.000409

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00131

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000943

Hom.:

Bravo

AF:

0.000521

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00182

AC:

ESP6500AA

AF:

0.000710

AC:

ESP6500EA

AF:

0.00118

AC:

ExAC

AF:

0.000635

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Oct 22, 2021

The c.404C>T (p.S135F) alteration is located in exon 2 (coding exon 2) of the SIGLEC6 gene. This alteration results from a C to T substitution at nucleotide position 404, causing the serine (S) at amino acid position 135 to be replaced by a phenylalanine (F). 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

0.21

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.57

Cadd

Benign

Dann

Uncertain

0.98

Eigen

Benign

-0.95

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.014

LIST_S2

Benign

0.054

T;T;T;T;T;T

M_CAP

Benign

0.0086

MetaRNN

Benign

0.018

T;T;T;T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.55

N;N;.;N;N;N

MutationTaster

Benign

1.0

N;N;N;N;N;N

PrimateAI

Benign

0.38

REVEL

Benign

0.082

Sift4G

Uncertain

0.012

D;D;D;D;D;D

Polyphen

0.47

P;.;.;P;B;B

Vest4

0.21

MVP

0.22

MPC

0.30

ClinPred

0.042

GERP RS

-4.5

Varity_R

0.13

gMVP

0.14

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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