12-108623244-C-T

Variant summary

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

The ENST00000550948.2(SELPLG):​c.1064G>A​(p.Arg355His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000168 in 1,610,438 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R355C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00017 ( 0 hom. )

Consequence

SELPLG
ENST00000550948.2 missense

Scores

1
5
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.242
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=0.18501723).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SELPLGNM_003006.4 linkuse as main transcriptc.1064G>A p.Arg355His missense_variant 2/2 ENST00000550948.2 NP_002997.2
SELPLGNM_001206609.2 linkuse as main transcriptc.1112G>A p.Arg371His missense_variant 2/2 NP_001193538.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SELPLGENST00000550948.2 linkuse as main transcriptc.1064G>A p.Arg355His missense_variant 2/21 NM_003006.4 ENSP00000447752 P2Q14242-1
SELPLGENST00000228463.6 linkuse as main transcriptc.1112G>A p.Arg371His missense_variant 2/22 ENSP00000228463 A2Q14242-2
SELPLGENST00000388962.4 linkuse as main transcriptc.1034G>A p.Arg345His missense_variant 2/25 ENSP00000373614 A2

Frequencies

GnomAD3 genomes
AF:
0.000139
AC:
21
AN:
150672
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000244
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:
0.000296
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000108
AC:
27
AN:
250848
Hom.:
0
AF XY:
0.0000885
AC XY:
12
AN XY:
135556
show subpopulations
Gnomad AFR exome
AF:
0.0000616
Gnomad AMR exome
AF:
0.0000290
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000212
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000171
AC:
250
AN:
1459766
Hom.:
0
Cov.:
31
AF XY:
0.000161
AC XY:
117
AN XY:
726210
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.0000674
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000581
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000210
Gnomad4 OTH exome
AF:
0.000133
GnomAD4 genome
AF:
0.000139
AC:
21
AN:
150672
Hom.:
0
Cov.:
33
AF XY:
0.000150
AC XY:
11
AN XY:
73550
show subpopulations
Gnomad4 AFR
AF:
0.0000244
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:
0.000296
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000198
Hom.:
0
Bravo
AF:
0.000121
TwinsUK
AF:
0.000539
AC:
2
ALSPAC
AF:
0.00
AC:
0
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000233
AC:
2
ExAC
AF:
0.000107
AC:
13
EpiCase
AF:
0.000437
EpiControl
AF:
0.000237

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 GeneticsNov 21, 2022The c.1064G>A (p.R355H) alteration is located in exon 2 (coding exon 1) of the SELPLG gene. This alteration results from a G to A substitution at nucleotide position 1064, causing the arginine (R) at amino acid position 355 to be replaced by a histidine (H). 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
0.22
BayesDel_addAF
Benign
-0.21
T
BayesDel_noAF
Benign
-0.23
CADD
Pathogenic
27
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.32
T;.;.
Eigen
Uncertain
0.27
Eigen_PC
Benign
0.20
FATHMM_MKL
Benign
0.24
N
LIST_S2
Uncertain
0.86
D;D;D
M_CAP
Benign
0.076
D
MetaRNN
Benign
0.19
T;T;T
MetaSVM
Benign
-0.79
T
MutationAssessor
Benign
1.9
L;.;.
MutationTaster
Benign
1.0
N;N;N
PrimateAI
Benign
0.41
T
PROVEAN
Uncertain
-2.9
D;D;D
REVEL
Benign
0.24
Sift
Uncertain
0.0030
D;D;D
Sift4G
Uncertain
0.0070
D;D;D
Polyphen
0.99
D;.;.
Vest4
0.23
MVP
0.91
MPC
0.59
ClinPred
0.35
T
GERP RS
4.0
Varity_R
0.12
gMVP
0.25

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: rs367836641; hg19: chr12-109017020; COSMIC: COSV57311886; API