rs16982743

Variant names:

• chr19-51501649-G-A
• rs16982743
• NM_053003.4:c.85C>T

Variant summary

Our verdict is Benign. The variant received -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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.04
• Publications: 34 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.328 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_053003.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIGLEC12	NM_053003.4	MANE Select	c.85C>T	p.Gln29*	stop_gained	Exon 1 of 8	NP_443729.1	Q96PQ1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIGLEC12	ENST00000291707.8	TSL:1 MANE Select	c.85C>T	p.Gln29*	stop_gained	Exon 1 of 8	ENSP00000291707.3	Q96PQ1-1
	SIGLEC12	ENST00000596742.1	TSL:1	n.85C>T		non_coding_transcript_exon	Exon 1 of 8	ENSP00000469791.1	M0QYF3
	SIGLEC12	ENST00000942370.1		c.85C>T	p.Gln29*	stop_gained	Exon 1 of 7	ENSP00000612429.1

Frequencies

GnomAD3 genomes AF: 0.217 AC: 32958 AN: 152000 Hom.: 4031 Cov.: 31

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

GnomAD2 exomes AF: 0.174 AC: 43847 AN: 251306 AF XY: 0.176

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 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.: 37 AF XY: 0.178 AC XY: 129653 AN XY: 727230

African (AFR) AF: 0.341 AC: 11405 AN: 33480

American (AMR) AF: 0.111 AC: 4966 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.203 AC: 5313 AN: 26136

East Asian (EAS) AF: 0.0351 AC: 1393 AN: 39700

South Asian (SAS) AF: 0.162 AC: 13994 AN: 86258

European-Finnish (FIN) AF: 0.187 AC: 10009 AN: 53412

Middle Eastern (MID) AF: 0.251 AC: 1450 AN: 5768

European-Non Finnish (NFE) AF: 0.180 AC: 200584 AN: 1111988

Other (OTH) AF: 0.187 AC: 11267 AN: 60396

GnomAD4 genome AF: 0.217 AC: 33010 AN: 152118 Hom.: 4047 Cov.: 31 AF XY: 0.214 AC XY: 15893 AN XY: 74374

African (AFR) AF: 0.333 AC: 13803 AN: 41434

American (AMR) AF: 0.149 AC: 2281 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.213 AC: 740 AN: 3472

East Asian (EAS) AF: 0.0449 AC: 233 AN: 5186

South Asian (SAS) AF: 0.143 AC: 692 AN: 4826

European-Finnish (FIN) AF: 0.186 AC: 1968 AN: 10606

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.184 AC: 12502 AN: 67986

Other (OTH) AF: 0.216 AC: 456 AN: 2108

Alfa AF: 0.199 Hom.: 9619

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.22
CADD	Pathogenic	35
DANN	Uncertain	0.99
Eigen	Benign	0.056
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.012	N
PhyloP100		1.0
Vest4		0.044
GERP RS		0.30
PromoterAI		-0.033	Neutral
Mutation Taster		=136/64	polymorphism (auto)

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

Other links and lift over

dbSNP: rs16982743; hg19: chr19-52004903; COSMIC: COSV52463822; COSMIC: COSV52463822;