1-169726764-G-C

Position:

• chr1-169726764-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000450.2(SELE):​c.1688C>G​(p.Ala563Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,461,578 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: SELE NM_000450.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0600

Genes affected

SELE (HGNC:10718): (selectin E) The protein encoded by this gene is found in cytokine-stimulated endothelial cells and is thought to be responsible for the accumulation of blood leukocytes at sites of inflammation by mediating the adhesion of cells to the vascular lining. It exhibits structural features such as the presence of lectin- and EGF-like domains followed by short consensus repeat (SCR) domains that contain 6 conserved cysteine residues. These proteins are part of the selectin family of cell adhesion molecules. Adhesion molecules participate in the interaction between leukocytes and the endothelium and appear to be involved in the pathogenesis of atherosclerosis. [provided by RefSeq, Jul 2008]

FIRRM (HGNC:25565): (FIGNL1 interacting regulator of recombination and mitosis)

ACMG classification

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=0.13637394).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SELE	NM_000450.2	c.1688C>G	p.Ala563Gly	missense_variant	11/14	ENST00000333360.12	NP_000441.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SELE	ENST00000333360.12	c.1688C>G	p.Ala563Gly	missense_variant	11/14	1	NM_000450.2	ENSP00000331736	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000411 AC: 6 AN: 1461578 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 727060

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 0.00000540

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 01, 2023

The c.1688C>G (p.A563G) alteration is located in exon 11 (coding exon 10) of the SELE gene. This alteration results from a C to G substitution at nucleotide position 1688, causing the alanine (A) at amino acid position 563 to be replaced by a glycine (G). 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	0.12
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	9.8
DANN	Benign	0.93
DEOGEN2	Benign	0.023	.;T;T;T;.
Eigen	Benign	-0.91
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.10	N
LIST_S2	Uncertain	0.88	D;D;D;D;D
M_CAP	Benign	0.0075	T
MetaRNN	Benign	0.14	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	.;.;.;L;.
MutationTaster	Benign	1.0	N;N;N;N;N;N;N;N;N
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.3	N;N;N;N;N
REVEL	Benign	0.059
Sift	Uncertain	0.0090	D;D;D;D;T
Sift4G	Uncertain	0.012	D;D;D;D;D
Polyphen		0.70	.;.;.;P;.
Vest4		0.30
MutPred		0.41		.;.;.;Gain of glycosylation at S562 (P = 0.0413);.;
MVP		0.36
MPC		0.15
ClinPred		0.24	T
GERP RS		-3.7
gMVP		0.36

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

Other links and lift over

dbSNP: rs1183533495; hg19: chr1-169695905;