chr12-108624122-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_003006.4(SELPLG):c.186G>A(p.Met62Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0843 in 1,614,010 control chromosomes in the GnomAD database, including 8,858 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.14 ( 2308 hom., cov: 32)

Exomes 𝑓: 0.078 ( 6550 hom. )

Consequence

SELPLG
NM_003006.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.977

Publications

65 publications found

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 was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004031837).

BP6

Variant 12-108624122-C-T is Benign according to our data. Variant chr12-108624122-C-T is described in ClinVar as Benign. ClinVar VariationId is 3055988.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SELPLG	NM_003006.4 link	c.186G>A	p.Met62Ile	missense_variant	Exon 2 of 2	ENST00000550948.2	NP_002997.2	Q14242-1
SELPLG	NM_001206609.2 link	c.234G>A	p.Met78Ile	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.186G>A	p.Met62Ile	missense_variant	Exon 2 of 2	1	NM_003006.4	ENSP00000447752.1	Q14242-1
SELPLG	ENST00000228463.7 link	c.234G>A	p.Met78Ile	missense_variant	Exon 2 of 2	2		ENSP00000228463.6	Q14242-2
SELPLG	ENST00000388962.4 link	c.186G>A	p.Met62Ile	missense_variant	Exon 1 of 2	5		ENSP00000373614.3	A0A0C4DFY0

Frequencies

GnomAD3 genomes

AF:

0.140

AC:

21285

AN:

152044

Hom.:

2301

Cov.:

show subpopulations

Gnomad AFR

AF:

0.282

Gnomad AMI

AF:

0.199

Gnomad AMR

AF:

0.128

Gnomad ASJ

AF:

0.144

Gnomad EAS

AF:

0.282

Gnomad SAS

AF:

0.0602

Gnomad FIN

AF:

0.0554

Gnomad MID

AF:

0.101

Gnomad NFE

AF:

0.0639

Gnomad OTH

AF:

0.125

GnomAD2 exomes

AF:

0.113

AC:

28525

AN:

251428

AF XY:

0.104

show subpopulations

Gnomad AFR exome

AF:

0.286

Gnomad AMR exome

AF:

0.167

Gnomad ASJ exome

AF:

0.152

Gnomad EAS exome

AF:

0.290

Gnomad FIN exome

AF:

0.0526

Gnomad NFE exome

AF:

0.0670

Gnomad OTH exome

AF:

0.101

GnomAD4 exome

AF:

0.0784

AC:

114658

AN:

1461848

Hom.:

6550

Cov.:

AF XY:

0.0770

AC XY:

55980

AN XY:

727232

show subpopulations

African (AFR)

AF:

0.284

AC:

9501

AN:

33476

American (AMR)

AF:

0.160

AC:

7148

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.155

AC:

4041

AN:

26136

East Asian (EAS)

AF:

0.258

AC:

10243

AN:

39700

South Asian (SAS)

AF:

0.0609

AC:

5256

AN:

86258

European-Finnish (FIN)

AF:

0.0533

AC:

2848

AN:

53418

Middle Eastern (MID)

AF:

0.111

AC:

638

AN:

5768

European-Non Finnish (NFE)

AF:

0.0622

AC:

69124

AN:

1111974

Other (OTH)

AF:

0.0970

AC:

5859

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

6384

12767

19151

25534

31918

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2914

5828

8742

11656

14570

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.140

AC:

21331

AN:

152162

Hom.:

2308

Cov.:

AF XY:

0.139

AC XY:

10306

AN XY:

74396

show subpopulations

African (AFR)

AF:

0.282

AC:

11703

AN:

41454

American (AMR)

AF:

0.128

AC:

1958

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.144

AC:

500

AN:

3464

East Asian (EAS)

AF:

0.283

AC:

1465

AN:

5178

South Asian (SAS)

AF:

0.0607

AC:

293

AN:

4828

European-Finnish (FIN)

AF:

0.0554

AC:

588

AN:

10612

Middle Eastern (MID)

AF:

0.116

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0639

AC:

4347

AN:

68014

Other (OTH)

AF:

0.124

AC:

262

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

865

1730

2596

3461

4326

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

214

428

642

856

1070

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0928

Hom.:

4444

Bravo

AF:

0.156

TwinsUK

AF:

0.0639

AC:

237

ALSPAC

AF:

0.0677

AC:

261

ESP6500AA

AF:

0.268

AC:

1181

ESP6500EA

AF:

0.0676

AC:

581

ExAC

AF:

0.113

AC:

13653

Asia WGS

AF:

0.148

AC:

514

AN:

3478

EpiCase

AF:

0.0702

EpiControl

AF:

0.0704

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

SELPLG-related disorder

Benign:1

Nov 04, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.84

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.064

(source)

DANN

Benign

0.51

DEOGEN2

Benign

0.034

T;.;.

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.26

T;T;T

MetaRNN

Benign

0.0040

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-0.58

N;.;.

PhyloP100

-0.98

PrimateAI

Benign

0.32

PROVEAN

Benign

0.070

N;N;N

REVEL

Benign

0.0040

Sift

Benign

1.0

T;T;T

Sift4G

Benign

0.78

T;T;T

Polyphen

0.0

B;.;.

Vest4

0.015

MutPred

0.32

Gain of catalytic residue at P59 (P = 2e-04);Gain of catalytic residue at P59 (P = 2e-04);.;

MPC

0.12

ClinPred

0.00058

GERP RS

-1.8

PromoterAI

-0.011

Neutral

(source)

Varity_R

0.020

gMVP

0.091

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over