Variant 12-108623591-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_003006.4(SELPLG):c.717G>A(p.Thr239=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00301 in 1,611,912 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0023 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0031 ( 13 hom. )

Consequence

SELPLG
NM_003006.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -12.8

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 -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 12-108623591-C-T is Benign according to our data. Variant chr12-108623591-C-T is described in ClinVar as [Benign]. Clinvar id is 718350.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-12.8 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SELPLG	NM_003006.4 linkuse as main transcript	c.717G>A	p.Thr239=	synonymous_variant	2/2	ENST00000550948.2	NP_002997.2
SELPLG	NM_001206609.2 linkuse as main transcript	c.765G>A	p.Thr255=	synonymous_variant	2/2		NP_001193538.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SELPLG	ENST00000550948.2 linkuse as main transcript	c.717G>A	p.Thr239=	synonymous_variant	2/2	1	NM_003006.4	ENSP00000447752	P2	Q14242-1
SELPLG	ENST00000228463.6 linkuse as main transcript	c.765G>A	p.Thr255=	synonymous_variant	2/2	2		ENSP00000228463	A2	Q14242-2
SELPLG	ENST00000388962.4 linkuse as main transcript	c.687G>A	p.Thr229=	synonymous_variant	2/2	5		ENSP00000373614	A2

Frequencies

GnomAD3 genomes

AF:

0.00233

AC:

352

AN:

150870

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00120

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00204

Gnomad ASJ

AF:

0.000289

Gnomad EAS

AF:

0.000195

Gnomad SAS

AF:

0.000421

Gnomad FIN

AF:

0.000192

Gnomad MID

AF:

0.00323

Gnomad NFE

AF:

0.00381

Gnomad OTH

AF:

0.00337

GnomAD3 exomes

AF:

0.00215

AC:

540

AN:

251460

Hom.:

AF XY:

0.00222

AC XY:

302

AN XY:

135898

show subpopulations

Gnomad AFR exome

AF:

0.00141

Gnomad AMR exome

AF:

0.00304

Gnomad ASJ exome

AF:

0.000298

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.00340

Gnomad OTH exome

AF:

0.00244

GnomAD4 exome

AF:

0.00308

AC:

4497

AN:

1460926

Hom.:

Cov.:

AF XY:

0.00300

AC XY:

2179

AN XY:

726840

show subpopulations

Gnomad4 AFR exome

AF:

0.000633

Gnomad4 AMR exome

AF:

0.00281

Gnomad4 ASJ exome

AF:

0.000306

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000116

Gnomad4 FIN exome

AF:

0.000243

Gnomad4 NFE exome

AF:

0.00375

Gnomad4 OTH exome

AF:

0.00234

GnomAD4 genome

AF:

0.00233

AC:

352

AN:

150986

Hom.:

Cov.:

AF XY:

0.00218

AC XY:

161

AN XY:

73758

show subpopulations

Gnomad4 AFR

AF:

0.00119

Gnomad4 AMR

AF:

0.00204

Gnomad4 ASJ

AF:

0.000289

Gnomad4 EAS

AF:

0.000196

Gnomad4 SAS

AF:

0.000421

Gnomad4 FIN

AF:

0.000192

Gnomad4 NFE

AF:

0.00381

Gnomad4 OTH

AF:

0.00333

Alfa

AF:

0.00276

Hom.:

Bravo

AF:

0.00248

EpiCase

AF:

0.00485

EpiControl

AF:

0.00373

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Apr 25, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

1.2

DANN

Benign

0.32

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over