Variant chr12-108623832-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_003006.4(SELPLG):c.476C>T(p.Thr159Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000448 in 1,585,656 control chromosomes in the GnomAD database, including 1 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000046 ( 1 hom. )

Consequence

SELPLG
NM_003006.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.38

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 -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.050121725).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SELPLG	NM_003006.4 link	c.476C>T	p.Thr159Met	missense_variant	2/2	ENST00000550948.2	NP_002997.2	Q14242-1
SELPLG	NM_001206609.2 link	c.524C>T	p.Thr175Met	missense_variant	2/2		NP_001193538.1	Q14242-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SELPLG	ENST00000550948.2 link	c.476C>T	p.Thr159Met	missense_variant	2/2	1	NM_003006.4	ENSP00000447752.1	Q14242-1
SELPLG	ENST00000228463.6 link	c.524C>T	p.Thr175Met	missense_variant	2/2	2		ENSP00000228463.6	Q14242-2
SELPLG	ENST00000388962.4 link	c.446C>T	p.Thr149Met	missense_variant	2/2	5		ENSP00000373614.3	A0A0C4DFY0

Frequencies

GnomAD3 genomes

AF:

0.0000330

AC:

AN:

151602

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000486

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000131

AC:

AN:

251404

Hom.:

AF XY:

0.000140

AC XY:

AN XY:

135860

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000781

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.0000460

AC:

AN:

1434054

Hom.:

Cov.:

AF XY:

0.0000450

AC XY:

AN XY:

711898

show subpopulations

Gnomad4 AFR exome

AF:

0.0000609

Gnomad4 AMR exome

AF:

0.000805

Gnomad4 ASJ exome

AF:

0.0000776

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000123

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000200

Gnomad4 OTH exome

AF:

0.0000508

GnomAD4 genome

AF:

0.0000330

AC:

AN:

151602

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74024

show subpopulations

Gnomad4 AFR

AF:

0.0000486

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.0000843

Hom.:

Bravo

AF:

0.0000529

ExAC

AF:

0.0000330

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 01, 2024

The c.476C>T (p.T159M) alteration is located in exon 2 (coding exon 1) of the SELPLG gene. This alteration results from a C to T substitution at nucleotide position 476, causing the threonine (T) at amino acid position 159 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.74

CADD

Benign

0.98

DANN

Benign

0.76

DEOGEN2

Benign

0.15

T;.;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.45

T;T;T

M_CAP

Benign

0.0035

MetaRNN

Benign

0.050

T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.3

L;.;.

PrimateAI

Benign

0.18

PROVEAN

Benign

-1.8

N;N;N

REVEL

Benign

0.011

Sift

Uncertain

0.011

D;D;D

Sift4G

Benign

0.12

T;T;T

Polyphen

0.37

B;.;.

Vest4

0.080

MutPred

0.27

Loss of glycosylation at T159 (P = 0.0057);.;.;

MVP

0.21

MPC

0.11

ClinPred

0.049

GERP RS

-1.9

Varity_R

0.025

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