12-108623395-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The ENST00000550948.2(SELPLG):​c.913G>A​(p.Val305Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0004 in 1,614,248 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00030 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00041 ( 9 hom. )

Consequence

SELPLG
ENST00000550948.2 missense

Scores

18

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -1.30
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0033406317).
BP6
Variant 12-108623395-C-T is Benign according to our data. Variant chr12-108623395-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3057867.Status of the report is no_assertion_criteria_provided, 0 stars.
BS2
High Homozygotes in GnomAdExome4 at 9 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SELPLGNM_003006.4 linkuse as main transcriptc.913G>A p.Val305Ile missense_variant 2/2 ENST00000550948.2 NP_002997.2
SELPLGNM_001206609.2 linkuse as main transcriptc.961G>A p.Val321Ile 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.913G>A p.Val305Ile missense_variant 2/21 NM_003006.4 ENSP00000447752 P2Q14242-1
SELPLGENST00000228463.6 linkuse as main transcriptc.961G>A p.Val321Ile missense_variant 2/22 ENSP00000228463 A2Q14242-2
SELPLGENST00000388962.4 linkuse as main transcriptc.883G>A p.Val295Ile missense_variant 2/25 ENSP00000373614 A2

Frequencies

GnomAD3 genomes
AF:
0.000282
AC:
43
AN:
152236
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000121
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000262
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00704
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000835
AC:
210
AN:
251454
Hom.:
3
AF XY:
0.00113
AC XY:
154
AN XY:
135898
show subpopulations
Gnomad AFR exome
AF:
0.000185
Gnomad AMR exome
AF:
0.000694
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.00588
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000879
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.000411
AC:
601
AN:
1461894
Hom.:
9
Cov.:
32
AF XY:
0.000598
AC XY:
435
AN XY:
727248
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.000581
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00611
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000171
Gnomad4 OTH exome
AF:
0.000430
GnomAD4 genome
AF:
0.000295
AC:
45
AN:
152354
Hom.:
0
Cov.:
33
AF XY:
0.000443
AC XY:
33
AN XY:
74500
show subpopulations
Gnomad4 AFR
AF:
0.000216
Gnomad4 AMR
AF:
0.000261
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00663
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000355
Hom.:
0
Bravo
AF:
0.0000907
ESP6500AA
AF:
0.000454
AC:
2
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.00104
AC:
126
Asia WGS
AF:
0.00231
AC:
8
AN:
3478

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

SELPLG-related disorder Benign:1
Likely benign, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesJan 11, 2021This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.072
BayesDel_addAF
Benign
-0.75
T
BayesDel_noAF
Benign
-0.85
CADD
Benign
0.88
DANN
Benign
0.72
DEOGEN2
Benign
0.049
T;.;.
Eigen
Benign
-1.4
Eigen_PC
Benign
-1.5
FATHMM_MKL
Benign
0.015
N
LIST_S2
Benign
0.30
T;T;T
MetaRNN
Benign
0.0033
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-0.14
N;.;.
MutationTaster
Benign
1.0
N;N;N
PrimateAI
Benign
0.26
T
PROVEAN
Benign
-0.44
N;N;N
REVEL
Benign
0.0060
Sift
Benign
0.88
T;T;T
Sift4G
Benign
0.48
T;T;T
Polyphen
0.23
B;.;.
Vest4
0.014
MVP
0.24
MPC
0.095
ClinPred
0.020
T
GERP RS
-1.3
Varity_R
0.012
gMVP
0.12

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: rs147978597; hg19: chr12-109017171; API