Variant rs16982743 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_053003.4(SIGLEC12):c.85C>T(p.Gln29*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 1,613,978 control chromosomes in the GnomAD database, including 28,548 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.22 ( 4047 hom., cov: 31)

Exomes 𝑓: 0.18 ( 24501 hom. )

Consequence

SIGLEC12
NM_053003.4 stop_gained

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.04

Variant links:

Genes affected

SIGLEC12 (HGNC:15482): (sialic acid binding Ig like lectin 12) Sialic acid-binding immunoglobulin-like lectins (SIGLECs) are a family of cell surface proteins belonging to the immunoglobulin superfamily. They mediate protein-carbohydrate interactions by selectively binding to different sialic acid moieties present on glycolipids and glycoproteins. This gene encodes a member of the SIGLEC3-like subfamily of SIGLECs. Members of this subfamily are characterized by an extracellular V-set immunoglobulin-like domain followed by two C2-set immunoglobulin-like domains, and the cytoplasmic tyrosine-based motifs ITIM and SLAM-like. The encoded protein, upon tyrosine phosphorylation, has been shown to recruit the Src homology 2 domain-containing protein-tyrosine phosphatases SHP1 and SHP2. It has been suggested that the protein is involved in the negative regulation of macrophage signaling by functioning as an inhibitory receptor. This gene is located in a cluster with other SIGLEC3-like genes on 19q13.4. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

SIGLEC12 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.328 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SIGLEC12	NM_053003.4 link	c.85C>T	p.Gln29*	stop_gained	1/8	ENST00000291707.8	NP_443729.1	Q96PQ1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SIGLEC12	ENST00000291707.8 link	c.85C>T	p.Gln29*	stop_gained	1/8	1	NM_053003.4	ENSP00000291707.3		Q96PQ1-1
SIGLEC12	ENST00000596742.1 link	n.85C>T		non_coding_transcript_exon_variant	1/8	1		ENSP00000469791.1		M0QYF3

Frequencies

GnomAD3 genomes

AF:

0.217

AC:

32958

AN:

152000

Hom.:

4031

Cov.:

show subpopulations

Gnomad AFR

AF:

0.333

Gnomad AMI

AF:

0.280

Gnomad AMR

AF:

0.149

Gnomad ASJ

AF:

0.213

Gnomad EAS

AF:

0.0448

Gnomad SAS

AF:

0.143

Gnomad FIN

AF:

0.186

Gnomad MID

AF:

0.294

Gnomad NFE

AF:

0.184

Gnomad OTH

AF:

0.206

GnomAD3 exomes

AF:

0.174

AC:

43847

AN:

251306

Hom.:

4344

AF XY:

0.176

AC XY:

23835

AN XY:

135808

show subpopulations

Gnomad AFR exome

AF:

0.334

Gnomad AMR exome

AF:

0.105

Gnomad ASJ exome

AF:

0.206

Gnomad EAS exome

AF:

0.0513

Gnomad SAS exome

AF:

0.160

Gnomad FIN exome

AF:

0.190

Gnomad NFE exome

AF:

0.190

Gnomad OTH exome

AF:

0.186

GnomAD4 exome

AF:

0.178

AC:

260381

AN:

1461860

Hom.:

24501

Cov.:

AF XY:

0.178

AC XY:

129653

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.341

Gnomad4 AMR exome

AF:

0.111

Gnomad4 ASJ exome

AF:

0.203

Gnomad4 EAS exome

AF:

0.0351

Gnomad4 SAS exome

AF:

0.162

Gnomad4 FIN exome

AF:

0.187

Gnomad4 NFE exome

AF:

0.180

Gnomad4 OTH exome

AF:

0.187

GnomAD4 genome

AF:

0.217

AC:

33010

AN:

152118

Hom.:

4047

Cov.:

AF XY:

0.214

AC XY:

15893

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.333

Gnomad4 AMR

AF:

0.149

Gnomad4 ASJ

AF:

0.213

Gnomad4 EAS

AF:

0.0449

Gnomad4 SAS

AF:

0.143

Gnomad4 FIN

AF:

0.186

Gnomad4 NFE

AF:

0.184

Gnomad4 OTH

AF:

0.216

Alfa

AF:

0.200

Hom.:

4326

Bravo

AF:

0.219

TwinsUK

AF:

0.174

AC:

646

ALSPAC

AF:

0.179

AC:

688

ESP6500AA

AF:

0.319

AC:

1404

ESP6500EA

AF:

0.190

AC:

1631

ExAC

AF:

0.180

AC:

21804

Asia WGS

AF:

0.137

AC:

482

AN:

3478

EpiCase

AF:

0.189

EpiControl

AF:

0.193

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.22

CADD

Pathogenic

DANN

Uncertain

0.99

Eigen

Benign

0.056

Eigen_PC

Benign

-0.40

FATHMM_MKL

Benign

0.012

Vest4

0.044

GERP RS

0.30

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over