12-108623488-T-C

Variant names:

• chr12-108623488-T-C
• rs7300972
• NM_003006.4:c.820A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003006.4(SELPLG):​c.820A>G​(p.Met274Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0334 in 1,614,150 control chromosomes in the GnomAD database, including 3,594 homozygotes. 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: 𝑓 0.092 (1603 hom., cov: 33)
  • Exomes 𝑓: 0.027 (1991 hom.)
• Consequence: SELPLG NM_003006.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.515
• Publications: 14 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.006195903).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.269 is higher than 0.05.

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.820A>G	p.Met274Val	missense	Exon 2 of 2	NP_002997.2	Q14242-1
	SELPLG	NM_001206609.2		c.868A>G	p.Met290Val	missense	Exon 2 of 2	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.820A>G	p.Met274Val	missense	Exon 2 of 2	ENSP00000447752.1	Q14242-1
	SELPLG	ENST00000228463.7	TSL:2	c.868A>G	p.Met290Val	missense	Exon 2 of 2	ENSP00000228463.6	Q14242-2
	SELPLG	ENST00000884614.1		c.820A>G	p.Met274Val	missense	Exon 2 of 2	ENSP00000554673.1

Frequencies

GnomAD3 genomes AF: 0.0923 AC: 14036 AN: 152140 Hom.: 1604 Cov.: 33

Gnomad AFR AF: 0.273

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0402

Gnomad ASJ AF: 0.00749

Gnomad EAS AF: 0.00231

Gnomad SAS AF: 0.0775

Gnomad FIN AF: 0.0406

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0168

Gnomad OTH AF: 0.0592

GnomAD2 exomes AF: 0.0440 AC: 11064 AN: 251450 AF XY: 0.0416

Gnomad AFR exome AF: 0.285

Gnomad AMR exome AF: 0.0233

Gnomad ASJ exome AF: 0.00794

Gnomad EAS exome AF: 0.000598

Gnomad FIN exome AF: 0.0416

Gnomad NFE exome AF: 0.0169

Gnomad OTH exome AF: 0.0269

GnomAD4 exome AF: 0.0273 AC: 39929 AN: 1461892 Hom.: 1991 Cov.: 32 AF XY: 0.0282 AC XY: 20538 AN XY: 727246

African (AFR) AF: 0.279 AC: 9350 AN: 33480

American (AMR) AF: 0.0240 AC: 1075 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00735 AC: 192 AN: 26136

East Asian (EAS) AF: 0.000655 AC: 26 AN: 39700

South Asian (SAS) AF: 0.0824 AC: 7106 AN: 86258

European-Finnish (FIN) AF: 0.0389 AC: 2076 AN: 53420

Middle Eastern (MID) AF: 0.0276 AC: 159 AN: 5768

European-Non Finnish (NFE) AF: 0.0161 AC: 17874 AN: 1112010

Other (OTH) AF: 0.0343 AC: 2071 AN: 60396

GnomAD4 genome AF: 0.0923 AC: 14061 AN: 152258 Hom.: 1603 Cov.: 33 AF XY: 0.0904 AC XY: 6733 AN XY: 74448

African (AFR) AF: 0.273 AC: 11330 AN: 41502

American (AMR) AF: 0.0401 AC: 614 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00749 AC: 26 AN: 3472

East Asian (EAS) AF: 0.00231 AC: 12 AN: 5186

South Asian (SAS) AF: 0.0768 AC: 370 AN: 4820

European-Finnish (FIN) AF: 0.0406 AC: 431 AN: 10622

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0168 AC: 1144 AN: 68028

Other (OTH) AF: 0.0605 AC: 128 AN: 2116

Alfa AF: 0.0365 Hom.: 1862

Bravo AF: 0.0988

TwinsUK AF: 0.0146 AC: 54

ALSPAC AF: 0.0176 AC: 68

ESP6500AA AF: 0.284 AC: 1251

ESP6500EA AF: 0.0185 AC: 159

ExAC AF: 0.0497 AC: 6038

Asia WGS AF: 0.0560 AC: 193 AN: 3478

EpiCase AF: 0.0148

EpiControl AF: 0.0152

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.76	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	7.8
DANN	Benign	0.72
DEOGEN2	Benign	0.048	T
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.090	N
LIST_S2	Benign	0.37	T
MetaRNN	Benign	0.0062	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.14	N
PhyloP100		0.52
PrimateAI	Benign	0.15	T
PROVEAN	Benign	0.23	N
REVEL	Benign	0.031
Sift	Uncertain	0.017	D
Sift4G	Benign	0.69	T
Polyphen		0.11	B
Vest4		0.022
MPC		0.14
ClinPred		0.0078	T
GERP RS		3.5
Varity_R		0.19
gMVP		0.082
Mutation Taster		=100/0	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: rs7300972; hg19: chr12-109017264; COSMIC: COSV57312584;