1-169596104-T-G

Variant summary

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

The NM_003005.4(SELP):ā€‹c.1922A>Cā€‹(p.Gln641Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,461,572 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q641R) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000062 ( 0 hom. )

Consequence

SELP
NM_003005.4 missense

Scores

2
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -5.08
Variant links:
Genes affected
SELP (HGNC:10721): (selectin P) This gene encodes a 140 kDa protein that is stored in the alpha-granules of platelets and Weibel-Palade bodies of endothelial cells. This protein redistributes to the plasma membrane during platelet activation and degranulation and mediates the interaction of activated endothelial cells or platelets with leukocytes. The membrane protein is a calcium-dependent receptor that binds to sialylated forms of Lewis blood group carbohydrate antigens on neutrophils and monocytes. Alternative splice variants may occur but are not well documented. [provided by RefSeq, Jul 2008]

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=0.098065645).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SELPNM_003005.4 linkc.1922A>C p.Gln641Pro missense_variant Exon 12 of 17 ENST00000263686.11 NP_002996.2 P16109Q6NUL9A0A024R8Y9

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SELPENST00000263686.11 linkc.1922A>C p.Gln641Pro missense_variant Exon 12 of 17 1 NM_003005.4 ENSP00000263686.5 P16109

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000279
AC:
7
AN:
251038
Hom.:
0
AF XY:
0.00000737
AC XY:
1
AN XY:
135658
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000203
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000616
AC:
9
AN:
1461572
Hom.:
0
Cov.:
31
AF XY:
0.00000275
AC XY:
2
AN XY:
727102
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000201
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000756
ExAC
AF:
0.0000165
AC:
2
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Sep 26, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1922A>C (p.Q641P) alteration is located in exon 12 (coding exon 12) of the SELP gene. This alteration results from a A to C substitution at nucleotide position 1922, causing the glutamine (Q) at amino acid position 641 to be replaced by a proline (P). 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
0.074
BayesDel_addAF
Benign
-0.38
T
BayesDel_noAF
Benign
-0.50
CADD
Benign
0.052
DANN
Benign
0.74
DEOGEN2
Benign
0.029
T;.;T;T;T
Eigen
Benign
-1.4
Eigen_PC
Benign
-1.6
FATHMM_MKL
Benign
0.74
D
LIST_S2
Benign
0.81
T;T;T;T;T
M_CAP
Benign
0.0047
T
MetaRNN
Benign
0.098
T;T;T;T;T
MetaSVM
Benign
-1.1
T
PrimateAI
Benign
0.21
T
PROVEAN
Benign
-2.4
N;N;D;.;D
REVEL
Benign
0.086
Sift
Uncertain
0.021
D;D;D;.;D
Sift4G
Uncertain
0.032
D;D;T;D;T
Vest4
0.21, 0.23, 0.25, 0.21
MutPred
0.39
.;Gain of glycosylation at Q641 (P = 0.017);.;.;.;
MVP
0.19
MPC
0.14
ClinPred
0.11
T
GERP RS
-7.3
gMVP
0.59

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs202164697; hg19: chr1-169565342; API