Genetic Variant SIGLEC10:p.Asn210Asp (chr19-51416744-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_033130.5(SIGLEC10):c.628A>G(p.Asn210Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 1,613,674 control chromosomes in the GnomAD database, including 11,657 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.094 ( 835 hom., cov: 32)

Exomes 𝑓: 0.12 ( 10822 hom. )

Consequence

SIGLEC10
NM_033130.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.32

Variant links:

Genes affected

SIGLEC10 (HGNC:15620): (sialic acid binding Ig like lectin 10) SIGLECs are members of the immunoglobulin superfamily that are expressed on the cell surface. Most SIGLECs have 1 or more cytoplasmic immune receptor tyrosine-based inhibitory motifs, or ITIMs. SIGLECs are typically expressed on cells of the innate immune system, with the exception of the B-cell expressed SIGLEC6 (MIM 604405).[supplied by OMIM, Jul 2002]

SIGLEC10 links:

SIGLEC10-AS1 (HGNC:40719): (SIGLEC10 antisense RNA 1)

SIGLEC10-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004534751).

BP6

Variant 19-51416744-T-C is Benign according to our data. Variant chr19-51416744-T-C is described in ClinVar as [Benign]. Clinvar id is 773360.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIGLEC10	NM_033130.5 link	c.628A>G	p.Asn210Asp	missense_variant	Exon 3 of 11	ENST00000339313.10	NP_149121.2	Q96LC7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIGLEC10	ENST00000339313.10 link	c.628A>G	p.Asn210Asp	missense_variant	Exon 3 of 11	1	NM_033130.5	ENSP00000345243.4		Q96LC7-1

Frequencies

GnomAD3 genomes

AF:

0.0938

AC:

14252

AN:

152006

Hom.:

835

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0355

Gnomad AMI

AF:

0.152

Gnomad AMR

AF:

0.0788

Gnomad ASJ

AF:

0.110

Gnomad EAS

AF:

0.0450

Gnomad SAS

AF:

0.144

Gnomad FIN

AF:

0.138

Gnomad MID

AF:

0.108

Gnomad NFE

AF:

0.124

Gnomad OTH

AF:

0.101

GnomAD3 exomes

AF:

0.105

AC:

25595

AN:

243034

Hom.:

1534

AF XY:

0.111

AC XY:

14526

AN XY:

131144

show subpopulations

Gnomad AFR exome

AF:

0.0327

Gnomad AMR exome

AF:

0.0595

Gnomad ASJ exome

AF:

0.107

Gnomad EAS exome

AF:

0.0473

Gnomad SAS exome

AF:

0.143

Gnomad FIN exome

AF:

0.134

Gnomad NFE exome

AF:

0.123

Gnomad OTH exome

AF:

0.110

GnomAD4 exome

AF:

0.118

AC:

172329

AN:

1461550

Hom.:

10822

Cov.:

100

AF XY:

0.119

AC XY:

86460

AN XY:

727052

show subpopulations

Gnomad4 AFR exome

AF:

0.0297

Gnomad4 AMR exome

AF:

0.0587

Gnomad4 ASJ exome

AF:

0.101

Gnomad4 EAS exome

AF:

0.0541

Gnomad4 SAS exome

AF:

0.130

Gnomad4 FIN exome

AF:

0.130

Gnomad4 NFE exome

AF:

0.125

Gnomad4 OTH exome

AF:

0.110

GnomAD4 genome

AF:

0.0937

AC:

14254

AN:

152124

Hom.:

835

Cov.:

AF XY:

0.0947

AC XY:

7039

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.0354

Gnomad4 AMR

AF:

0.0787

Gnomad4 ASJ

AF:

0.110

Gnomad4 EAS

AF:

0.0453

Gnomad4 SAS

AF:

0.145

Gnomad4 FIN

AF:

0.138

Gnomad4 NFE

AF:

0.124

Gnomad4 OTH

AF:

0.100

Alfa

AF:

0.107

Hom.:

439

Bravo

AF:

0.0855

ESP6500AA

AF:

0.0363

AC:

160

ESP6500EA

AF:

0.114

AC:

984

ExAC

AF:

0.105

AC:

12736

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jul 26, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.055

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.51

CADD

Benign

0.053

DANN

Benign

0.56

DEOGEN2

Benign

0.089

.;.;.;.;.;.;T;.;T

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.00068

LIST_S2

Benign

0.22

T;T;T;T;T;T;T;T;T

MetaRNN

Benign

0.0045

T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-0.65

.;N;.;.;.;.;N;.;.

PrimateAI

Benign

0.23

PROVEAN

Benign

0.44

N;N;N;N;N;N;N;N;N

REVEL

Benign

0.18

Sift

Benign

1.0

T;T;T;T;T;T;T;T;T

Sift4G

Benign

0.58

T;T;T;T;T;T;T;.;.

Polyphen

0.0

B;B;.;B;.;B;B;.;.

Vest4

0.093

ClinPred

0.000019

GERP RS

-0.23

Varity_R

0.030

gMVP

0.19

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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