Genetic Variant SIGLEC10:p.Lys314Arg (chr19-51415981-T-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_033130.5(SIGLEC10):c.941A>G(p.Lys314Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00737 in 1,599,404 control chromosomes in the GnomAD database, including 112 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.0087 ( 10 hom., cov: 32)

Exomes 𝑓: 0.0072 ( 102 hom. )

Consequence

SIGLEC10
NM_033130.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0290

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004564494).

BP6

Variant 19-51415981-T-C is Benign according to our data. Variant chr19-51415981-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2650375.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIGLEC10	NM_033130.5 link	c.941A>G	p.Lys314Arg	missense_variant	Exon 5 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.941A>G	p.Lys314Arg	missense_variant	Exon 5 of 11	1	NM_033130.5	ENSP00000345243.4		Q96LC7-1

Frequencies

GnomAD3 genomes

AF:

0.00874

AC:

1328

AN:

151860

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00293

Gnomad AMI

AF:

0.0340

Gnomad AMR

AF:

0.00459

Gnomad ASJ

AF:

0.00404

Gnomad EAS

AF:

0.000582

Gnomad SAS

AF:

0.00561

Gnomad FIN

AF:

0.0117

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0134

Gnomad OTH

AF:

0.0120

GnomAD3 exomes

AF:

0.00414

AC:

1029

AN:

248786

Hom.:

AF XY:

0.00422

AC XY:

568

AN XY:

134550

show subpopulations

Gnomad AFR exome

AF:

0.00136

Gnomad AMR exome

AF:

0.00296

Gnomad ASJ exome

AF:

0.00160

Gnomad EAS exome

AF:

0.000218

Gnomad SAS exome

AF:

0.00250

Gnomad FIN exome

AF:

0.00554

Gnomad NFE exome

AF:

0.00592

Gnomad OTH exome

AF:

0.00460

GnomAD4 exome

AF:

0.00723

AC:

10459

AN:

1447426

Hom.:

102

Cov.:

AF XY:

0.00712

AC XY:

5125

AN XY:

720088

show subpopulations

Gnomad4 AFR exome

AF:

0.00201

Gnomad4 AMR exome

AF:

0.00294

Gnomad4 ASJ exome

AF:

0.00177

Gnomad4 EAS exome

AF:

0.000504

Gnomad4 SAS exome

AF:

0.00342

Gnomad4 FIN exome

AF:

0.0114

Gnomad4 NFE exome

AF:

0.00800

Gnomad4 OTH exome

AF:

0.00745

GnomAD4 genome

AF:

0.00874

AC:

1328

AN:

151978

Hom.:

Cov.:

AF XY:

0.00828

AC XY:

615

AN XY:

74280

show subpopulations

Gnomad4 AFR

AF:

0.00292

Gnomad4 AMR

AF:

0.00458

Gnomad4 ASJ

AF:

0.00404

Gnomad4 EAS

AF:

0.000583

Gnomad4 SAS

AF:

0.00561

Gnomad4 FIN

AF:

0.0117

Gnomad4 NFE

AF:

0.0134

Gnomad4 OTH

AF:

0.0119

Alfa

AF:

0.00678

Hom.:

ExAC

AF:

0.00799

AC:

970

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Feb 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

SIGLEC10: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.52

CADD

Benign

3.8

DANN

Benign

0.84

DEOGEN2

Benign

0.079

.;.;.;.;T;.

Eigen

Benign

-0.94

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.0086

LIST_S2

Benign

0.12

T;T;T;T;T;T

MetaRNN

Benign

0.0046

T;T;T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.66

.;N;.;.;N;.

PrimateAI

Benign

0.40

PROVEAN

Benign

-2.0

N;N;N;N;N;N

REVEL

Benign

0.072

Sift

Benign

0.39

T;T;T;T;T;T

Sift4G

Benign

0.31

T;T;T;T;T;.

Polyphen

0.18

B;P;.;B;B;.

Vest4

0.074

MVP

0.25

ClinPred

0.0076

GERP RS

-1.6

Varity_R

0.092

gMVP

0.16

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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