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GeneBe

12-108623772-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003006.4(SELPLG):c.536C>T(p.Thr179Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000298 in 1,612,336 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

SELPLG
NM_003006.4 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.26
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.10102433).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SELPLGNM_003006.4 linkuse as main transcriptc.536C>T p.Thr179Met missense_variant 2/2 ENST00000550948.2
SELPLGNM_001206609.2 linkuse as main transcriptc.584C>T p.Thr195Met missense_variant 2/2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SELPLGENST00000550948.2 linkuse as main transcriptc.536C>T p.Thr179Met missense_variant 2/21 NM_003006.4 P2Q14242-1
SELPLGENST00000228463.6 linkuse as main transcriptc.584C>T p.Thr195Met missense_variant 2/22 A2Q14242-2
SELPLGENST00000388962.4 linkuse as main transcriptc.506C>T p.Thr169Met missense_variant 2/25 A2

Frequencies

GnomAD3 genomes
AF:
0.0000595
AC:
9
AN:
151322
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000219
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000279
AC:
7
AN:
251278
Hom.:
0
AF XY:
0.0000368
AC XY:
5
AN XY:
135798
show subpopulations
Gnomad AFR exome
AF:
0.000185
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.0000653
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000880
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000267
AC:
39
AN:
1461014
Hom.:
0
Cov.:
32
AF XY:
0.0000275
AC XY:
20
AN XY:
726778
show subpopulations
Gnomad4 AFR exome
AF:
0.0000300
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.0000581
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000288
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000595
AC:
9
AN:
151322
Hom.:
0
Cov.:
32
AF XY:
0.0000406
AC XY:
3
AN XY:
73872
show subpopulations
Gnomad4 AFR
AF:
0.000219
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:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000354
Hom.:
0
ExAC
AF:
0.0000330
AC:
4

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 submitterclinical testingAmbry GeneticsJun 06, 2023The c.536C>T (p.T179M) 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 536, causing the threonine (T) at amino acid position 179 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
0.090
BayesDel_addAF
Benign
-0.48
T
BayesDel_noAF
Benign
-0.65
Cadd
Benign
7.1
Dann
Benign
0.77
DEOGEN2
Benign
0.15
T;.;.
Eigen
Benign
-0.39
Eigen_PC
Benign
-0.52
FATHMM_MKL
Benign
0.24
N
LIST_S2
Benign
0.66
T;T;T
M_CAP
Benign
0.0052
T
MetaRNN
Benign
0.10
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.94
L;.;.
MutationTaster
Benign
1.0
N;N;N
PrimateAI
Benign
0.19
T
PROVEAN
Benign
-2.3
N;D;N
REVEL
Benign
0.051
Sift
Benign
0.26
T;T;T
Sift4G
Benign
0.12
T;T;T
Polyphen
0.94
P;.;.
Vest4
0.10
MutPred
0.34
Gain of catalytic residue at P175 (P = 0.0011);.;.;
MVP
0.51
MPC
0.11
ClinPred
0.062
T
GERP RS
1.6
Varity_R
0.017
gMVP
0.20

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.

Other links and lift over

dbSNP: rs765784409; hg19: chr12-109017548; API