12-108623771-CGT-GCG

Variant names:

• chr12-108623771-CGT-GCG
• NM_003006.4:c.535_537delACGinsCGC
• SELPLG p.Thr179Arg

Variant summary

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

The NM_003006.4(SELPLG):​c.535_537delACGinsCGC​(p.Thr179Arg) 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. T179M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SELPLG NM_003006.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00500
• Publications: 0 publications found

Genes affected

SELPLG (HGNC:10722): (selectin P ligand) This gene encodes a glycoprotein that functions as a high affinity counter-receptor for the cell adhesion molecules P-, E- and L- selectin expressed on myeloid cells and stimulated T lymphocytes. As such, this protein plays a critical role in leukocyte trafficking during inflammation by tethering of leukocytes to activated platelets or endothelia expressing selectins. This protein requires two post-translational modifications, tyrosine sulfation and the addition of the sialyl Lewis x tetrasaccharide (sLex) to its O-linked glycans, for its high-affinity binding activity. Aberrant expression of this gene and polymorphisms in this gene are associated with defects in the innate and adaptive immune response. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Apr 2011]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003006.4. 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
	SELPLG	NM_003006.4	MANE Select	c.535_537delACGinsCGC	p.Thr179Arg	missense	N/A	NP_002997.2	Q14242-1
	SELPLG	NM_001206609.2		c.583_585delACGinsCGC	p.Thr195Arg	missense	N/A	NP_001193538.1	Q14242-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SELPLG	ENST00000550948.2	TSL:1 MANE Select	c.535_537delACGinsCGC	p.Thr179Arg	missense	N/A	ENSP00000447752.1	Q14242-1
	SELPLG	ENST00000228463.7	TSL:2	c.583_585delACGinsCGC	p.Thr195Arg	missense	N/A	ENSP00000228463.6	Q14242-2
	SELPLG	ENST00000884614.1		c.535_537delACGinsCGC	p.Thr179Arg	missense	N/A	ENSP00000554673.1

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		-0.0050

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: chr12-109017547;