Variant rs66949844 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_053003.4(SIGLEC12):c.196_197insG(p.Ala66GlyfsTer50) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.654 in 1,613,324 control chromosomes in the GnomAD database, including 348,684 homozygotes. Variant has been reported in ClinVar as Benign (★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.64 ( 31498 hom., cov: 0)

Exomes 𝑓: 0.66 ( 317186 hom. )

Consequence

SIGLEC12
NM_053003.4 frameshift

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.462

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 -10 ACMG points.

BP6

Variant 19-51501537-G-GC is Benign according to our data. Variant chr19-51501537-G-GC is described in ClinVar as [Benign]. Clinvar id is 403443.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.709 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SIGLEC12	NM_053003.4 linkuse as main transcript	c.196_197insG	p.Ala66GlyfsTer50	frameshift_variant	1/8	ENST00000291707.8	NP_443729.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SIGLEC12	ENST00000291707.8 linkuse as main transcript	c.196_197insG	p.Ala66GlyfsTer50	frameshift_variant	1/8	1	NM_053003.4	ENSP00000291707	P1	Q96PQ1-1
SIGLEC12	ENST00000596742.1 linkuse as main transcript	c.196_197insG	p.Ala66GlyfsTer50	frameshift_variant, NMD_transcript_variant	1/8	1		ENSP00000469791

Frequencies

GnomAD3 genomes

AF:

0.640

AC:

96901

AN:

151404

Hom.:

31491

Cov.:

show subpopulations

Gnomad AFR

AF:

0.592

Gnomad AMI

AF:

0.619

Gnomad AMR

AF:

0.720

Gnomad ASJ

AF:

0.585

Gnomad EAS

AF:

0.371

Gnomad SAS

AF:

0.638

Gnomad FIN

AF:

0.659

Gnomad MID

AF:

0.653

Gnomad NFE

AF:

0.671

Gnomad OTH

AF:

0.666

GnomAD3 exomes

AF:

0.645

AC:

162121

AN:

251402

Hom.:

53484

AF XY:

0.642

AC XY:

87193

AN XY:

135868

show subpopulations

Gnomad AFR exome

AF:

0.591

Gnomad AMR exome

AF:

0.773

Gnomad ASJ exome

AF:

0.587

Gnomad EAS exome

AF:

0.351

Gnomad SAS exome

AF:

0.621

Gnomad FIN exome

AF:

0.668

Gnomad NFE exome

AF:

0.668

Gnomad OTH exome

AF:

0.653

GnomAD4 exome

AF:

0.656

AC:

958732

AN:

1461802

Hom.:

317186

Cov.:

AF XY:

0.655

AC XY:

476047

AN XY:

727202

show subpopulations

Gnomad4 AFR exome

AF:

0.585

Gnomad4 AMR exome

AF:

0.764

Gnomad4 ASJ exome

AF:

0.589

Gnomad4 EAS exome

AF:

0.375

Gnomad4 SAS exome

AF:

0.623

Gnomad4 FIN exome

AF:

0.662

Gnomad4 NFE exome

AF:

0.668

Gnomad4 OTH exome

AF:

0.642

GnomAD4 genome

AF:

0.640

AC:

96931

AN:

151522

Hom.:

31498

Cov.:

AF XY:

0.637

AC XY:

47132

AN XY:

73994

show subpopulations

Gnomad4 AFR

AF:

0.591

Gnomad4 AMR

AF:

0.720

Gnomad4 ASJ

AF:

0.585

Gnomad4 EAS

AF:

0.370

Gnomad4 SAS

AF:

0.637

Gnomad4 FIN

AF:

0.659

Gnomad4 NFE

AF:

0.671

Gnomad4 OTH

AF:

0.660

Alfa

AF:

0.649

Hom.:

5834

Bravo

AF:

0.643

Asia WGS

AF:

0.538

AC:

1870

AN:

3478

EpiCase

AF:

0.670

EpiControl

AF:

0.669

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency in ESP (all): 8141/12518=65% -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over