Genetic Variant SIGLEC10:p.Val313Val (chr19-51415983-C-T) – 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.939G>A(p.Val313Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00751 in 1,600,040 control chromosomes in the GnomAD database, including 112 homozygotes. In-silico tool predicts 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: 0.0074 ( 102 hom. )

Consequence

SIGLEC10
NM_033130.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.588

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=-0.81).

BP6

Variant 19-51415983-C-T is Benign according to our data. Variant chr19-51415983-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2650376.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.588 with no splicing effect.

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.939G>A	p.Val313Val	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.939G>A	p.Val313Val	synonymous_variant	Exon 5 of 11	1	NM_033130.5	ENSP00000345243.4		Q96LC7-1

Frequencies

GnomAD3 genomes

AF:

0.00875

AC:

1330

AN:

152036

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00295

Gnomad AMI

AF:

0.0340

Gnomad AMR

AF:

0.00459

Gnomad ASJ

AF:

0.00403

Gnomad EAS

AF:

0.000580

Gnomad SAS

AF:

0.00559

Gnomad FIN

AF:

0.0115

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0134

Gnomad OTH

AF:

0.0120

GnomAD3 exomes

AF:

0.00442

AC:

1101

AN:

248868

Hom.:

AF XY:

0.00451

AC XY:

607

AN XY:

134612

show subpopulations

Gnomad AFR exome

AF:

0.00124

Gnomad AMR exome

AF:

0.00313

Gnomad ASJ exome

AF:

0.00209

Gnomad EAS exome

AF:

0.000217

Gnomad SAS exome

AF:

0.00263

Gnomad FIN exome

AF:

0.00568

Gnomad NFE exome

AF:

0.00640

Gnomad OTH exome

AF:

0.00493

GnomAD4 exome

AF:

0.00738

AC:

10680

AN:

1447886

Hom.:

102

Cov.:

AF XY:

0.00725

AC XY:

5219

AN XY:

720304

show subpopulations

Gnomad4 AFR exome

AF:

0.00204

Gnomad4 AMR exome

AF:

0.00296

Gnomad4 ASJ exome

AF:

0.00188

Gnomad4 EAS exome

AF:

0.000504

Gnomad4 SAS exome

AF:

0.00347

Gnomad4 FIN exome

AF:

0.0115

Gnomad4 NFE exome

AF:

0.00818

Gnomad4 OTH exome

AF:

0.00763

GnomAD4 genome

AF:

0.00874

AC:

1330

AN:

152154

Hom.:

Cov.:

AF XY:

0.00832

AC XY:

619

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.00294

Gnomad4 AMR

AF:

0.00458

Gnomad4 ASJ

AF:

0.00403

Gnomad4 EAS

AF:

0.000581

Gnomad4 SAS

AF:

0.00560

Gnomad4 FIN

AF:

0.0115

Gnomad4 NFE

AF:

0.0134

Gnomad4 OTH

AF:

0.0118

Alfa

AF:

0.00681

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

-0.81

CADD

Benign

DANN

Benign

0.77

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