Genetic Variant SELPLG:p.Met274Val (chr12-108623488-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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. 14/20 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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.515

Variant links:

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]

SELPLG links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SELPLG	NM_003006.4 link	c.820A>G	p.Met274Val	missense_variant	Exon 2 of 2	ENST00000550948.2	NP_002997.2	Q14242-1
SELPLG	NM_001206609.2 link	c.868A>G	p.Met290Val	missense_variant	Exon 2 of 2		NP_001193538.1	Q14242-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SELPLG	ENST00000550948.2 link	c.820A>G	p.Met274Val	missense_variant	Exon 2 of 2	1	NM_003006.4	ENSP00000447752.1	Q14242-1
SELPLG	ENST00000228463.6 link	c.868A>G	p.Met290Val	missense_variant	Exon 2 of 2	2		ENSP00000228463.6	Q14242-2
SELPLG	ENST00000388962.4 link	c.790A>G	p.Met264Val	missense_variant	Exon 2 of 2	5		ENSP00000373614.3	A0A0C4DFY0

Frequencies

GnomAD3 genomes

AF:

0.0923

AC:

14036

AN:

152140

Hom.:

1604

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.0440

AC:

11064

AN:

251450

Hom.:

853

AF XY:

0.0416

AC XY:

5660

AN XY:

135900

show subpopulations

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 SAS exome

AF:

0.0832

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.:

AF XY:

0.0282

AC XY:

20538

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.279

Gnomad4 AMR exome

AF:

0.0240

Gnomad4 ASJ exome

AF:

0.00735

Gnomad4 EAS exome

AF:

0.000655

Gnomad4 SAS exome

AF:

0.0824

Gnomad4 FIN exome

AF:

0.0389

Gnomad4 NFE exome

AF:

0.0161

Gnomad4 OTH exome

AF:

0.0343

GnomAD4 genome

AF:

0.0923

AC:

14061

AN:

152258

Hom.:

1603

Cov.:

AF XY:

0.0904

AC XY:

6733

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.273

Gnomad4 AMR

AF:

0.0401

Gnomad4 ASJ

AF:

0.00749

Gnomad4 EAS

AF:

0.00231

Gnomad4 SAS

AF:

0.0768

Gnomad4 FIN

AF:

0.0406

Gnomad4 NFE

AF:

0.0168

Gnomad4 OTH

AF:

0.0605

Alfa

AF:

0.0262

Hom.:

556

Bravo

AF:

0.0988

TwinsUK

AF:

0.0146

AC:

ALSPAC

AF:

0.0176

AC:

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 v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.76

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

LIST_S2

Benign

0.37

T;T;T

MetaRNN

Benign

0.0062

T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.14

N;.;.

PrimateAI

Benign

0.15

PROVEAN

Benign

0.23

N;N;N

REVEL

Benign

0.031

Sift

Uncertain

0.017

D;D;T

Sift4G

Benign

0.69

T;T;T

Polyphen

0.11

B;.;.

Vest4

0.022

MPC

0.14

ClinPred

0.0078

GERP RS

3.5

Varity_R

0.19

gMVP

0.082

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over