12-108623892-G-A

Position:

chr12-108623892-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The ENST00000550948.2(SELPLG):c.416C>T(p.Thr139Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000113 in 1,067,066 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. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000076 ( 0 hom., cov: 28)

Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

SELPLG
ENST00000550948.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.47

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0627552).

BP6

Variant 12-108623892-G-A is Benign according to our data. Variant chr12-108623892-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2520905.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SELPLG	NM_003006.4 linkuse as main transcript	c.416C>T	p.Thr139Met	missense_variant	2/2	ENST00000550948.2	NP_002997.2
SELPLG	NM_001206609.2 linkuse as main transcript	c.464C>T	p.Thr155Met	missense_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.416C>T	p.Thr139Met	missense_variant	2/2	1	NM_003006.4	ENSP00000447752	P2	Q14242-1
SELPLG	ENST00000228463.6 linkuse as main transcript	c.464C>T	p.Thr155Met	missense_variant	2/2	2		ENSP00000228463	A2	Q14242-2
SELPLG	ENST00000388962.4 linkuse as main transcript	c.391-5C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		5		ENSP00000373614	A2

Frequencies

GnomAD3 genomes

AF:

0.0000759

AC:

AN:

105428

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000633

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000932

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000442

Gnomad OTH

AF:

0.00133

GnomAD3 exomes

AF:

0.0000601

AC:

AN:

249782

Hom.:

AF XY:

0.0000444

AC XY:

AN XY:

134990

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000110

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000885

Gnomad OTH exome

AF:

0.000493

GnomAD4 exome

AF:

0.000118

AC:

113

AN:

961594

Hom.:

Cov.:

AF XY:

0.000115

AC XY:

AN XY:

476698

show subpopulations

Gnomad4 AFR exome

AF:

0.000117

Gnomad4 AMR exome

AF:

0.0000284

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000345

Gnomad4 SAS exome

AF:

0.0000388

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000114

Gnomad4 OTH exome

AF:

0.000453

GnomAD4 genome

AF:

0.0000758

AC:

AN:

105472

Hom.:

Cov.:

AF XY:

0.0000780

AC XY:

AN XY:

51288

show subpopulations

Gnomad4 AFR

AF:

0.0000632

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000935

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000442

Gnomad4 OTH

AF:

0.00133

Alfa

AF:

0.0000580

Hom.:

Bravo

AF:

0.0000529

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000121

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 05, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.73

CADD

Benign

0.19

DANN

Benign

0.94

DEOGEN2

Benign

0.084

T;.

Eigen

Benign

-0.85

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.099

LIST_S2

Benign

0.41

T;T

M_CAP

Benign

0.0033

MetaRNN

Benign

0.063

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

L;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.16

PROVEAN

Benign

-1.2

N;N

REVEL

Benign

0.094

Sift

Benign

0.26

T;T

Sift4G

Benign

0.099

T;T

Polyphen

0.99

D;.

Vest4

0.091

MVP

0.36

MPC

0.11

ClinPred

0.031

GERP RS

-1.3

Varity_R

0.015

gMVP

0.15

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