19-51496931-CAC-GAG

Variant names:

• chr19-51496931-CAC-GAG
• NM_053003.4:c.1546_1548delGTGinsCTC
• SIGLEC12 p.Val516Leu

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_053003.4(SIGLEC12):​c.1546_1548delGTGinsCTC​(p.Val516Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SIGLEC12 NM_053003.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.141
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

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.1546_1548delGTGinsCTC	p.Val516Leu	missense	N/A	NP_443729.1	Q96PQ1-1
	SIGLEC12	NM_033329.2		c.1192_1194delGTGinsCTC	p.Val398Leu	missense	N/A	NP_201586.1	Q96PQ1-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIGLEC12	ENST00000291707.8	TSL:1 MANE Select	c.1546_1548delGTGinsCTC	p.Val516Leu	missense	N/A	ENSP00000291707.3	Q96PQ1-1
	SIGLEC12	ENST00000596742.1	TSL:1	n.*761_*763delGTGinsCTC		non_coding_transcript_exon	Exon 7 of 8	ENSP00000469791.1	M0QYF3
	SIGLEC12	ENST00000596742.1	TSL:1	n.*761_*763delGTGinsCTC		3_prime_UTR	Exon 7 of 8	ENSP00000469791.1	M0QYF3

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.14

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr19-52000185;