rs7300972

Positions:

• chr12-108623488-T-A
• chr12-108623488-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003006.4(SELPLG):​c.820A>T​(p.Met274Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: SELPLG NM_003006.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.515

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08555618).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SELPLG	NM_003006.4	c.820A>T	p.Met274Leu	missense_variant	2/2	ENST00000550948.2
SELPLG	NM_001206609.2	c.868A>T	p.Met290Leu	missense_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SELPLG	ENST00000550948.2	c.820A>T	p.Met274Leu	missense_variant	2/2	1	NM_003006.4	P2
SELPLG	ENST00000228463.6	c.868A>T	p.Met290Leu	missense_variant	2/2	2		A2
SELPLG	ENST00000388962.4	c.790A>T	p.Met264Leu	missense_variant	2/2	5		A2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000410 AC: 6 AN: 1461892 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 727246

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000540

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	14
DANN	Benign	0.76
DEOGEN2	Benign	0.060	T;.;.
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.35	T;T;T
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.086	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N;.;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.15	T
PROVEAN	Benign	-0.23	N;N;N
REVEL	Benign	0.019
Sift	Uncertain	0.019	D;D;T
Sift4G	Benign	0.99	T;T;T
Polyphen		0.11	B;.;.
Vest4		0.085
MutPred		0.25		Gain of glycosylation at S273 (P = 0.0306);.;.;
MVP		0.35
MPC		0.11
ClinPred		0.18	T
GERP RS		3.5
Varity_R		0.22
gMVP		0.065

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

Other links and lift over

dbSNP: rs7300972; hg19: chr12-109017264;