Genetic Variant SIGLEC10:p.Ala315Ala (chr19-51415977-A-G) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_033130.5(SIGLEC10):c.945T>C(p.Ala315Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00691 in 1,597,556 control chromosomes in the GnomAD database, including 114 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0089 ( 9 hom., cov: 32)

Exomes 𝑓: 0.0067 ( 105 hom. )

Consequence

SIGLEC10
NM_033130.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.29

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 -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BP6

Variant 19-51415977-A-G is Benign according to our data. Variant chr19-51415977-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2650374.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-2.29 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIGLEC10	NM_033130.5 link	c.945T>C	p.Ala315Ala	synonymous_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.945T>C	p.Ala315Ala	synonymous_variant	Exon 5 of 11	1	NM_033130.5	ENSP00000345243.4		Q96LC7-1

Frequencies

GnomAD3 genomes

AF:

0.00886

AC:

1346

AN:

151888

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00295

Gnomad AMI

AF:

0.0340

Gnomad AMR

AF:

0.00518

Gnomad ASJ

AF:

0.00403

Gnomad EAS

AF:

0.000583

Gnomad SAS

AF:

0.00602

Gnomad FIN

AF:

0.0116

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0135

Gnomad OTH

AF:

0.0125

GnomAD3 exomes

AF:

0.00420

AC:

1045

AN:

248860

Hom.:

AF XY:

0.00430

AC XY:

578

AN XY:

134546

show subpopulations

Gnomad AFR exome

AF:

0.00142

Gnomad AMR exome

AF:

0.00314

Gnomad ASJ exome

AF:

0.00140

Gnomad EAS exome

AF:

0.000217

Gnomad SAS exome

AF:

0.00259

Gnomad FIN exome

AF:

0.00591

Gnomad NFE exome

AF:

0.00593

Gnomad OTH exome

AF:

0.00444

GnomAD4 exome

AF:

0.00671

AC:

9698

AN:

1445550

Hom.:

105

Cov.:

AF XY:

0.00666

AC XY:

4789

AN XY:

719212

show subpopulations

Gnomad4 AFR exome

AF:

0.00198

Gnomad4 AMR exome

AF:

0.00312

Gnomad4 ASJ exome

AF:

0.00177

Gnomad4 EAS exome

AF:

0.000529

Gnomad4 SAS exome

AF:

0.00340

Gnomad4 FIN exome

AF:

0.0115

Gnomad4 NFE exome

AF:

0.00733

Gnomad4 OTH exome

AF:

0.00719

GnomAD4 genome

AF:

0.00885

AC:

1346

AN:

152006

Hom.:

Cov.:

AF XY:

0.00841

AC XY:

625

AN XY:

74296

show subpopulations

Gnomad4 AFR

AF:

0.00294

Gnomad4 AMR

AF:

0.00518

Gnomad4 ASJ

AF:

0.00403

Gnomad4 EAS

AF:

0.000584

Gnomad4 SAS

AF:

0.00602

Gnomad4 FIN

AF:

0.0116

Gnomad4 NFE

AF:

0.0135

Gnomad4 OTH

AF:

0.0123

Alfa

AF:

0.00770

Hom.:

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, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.14

DANN

Benign

0.43

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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