1-169727892-C-T

Variant names:

• chr1-169727892-C-T
• NM_000450.2:c.1315G>A

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_000450.2(SELE):​c.1315G>A​(p.Gly439Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,772 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SELE NM_000450.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.74
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.903

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000450.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SELE	NM_000450.2	MANE Select	c.1315G>A	p.Gly439Ser	missense	Exon 9 of 14	NP_000441.2	P16581

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SELE	ENST00000333360.12	TSL:1 MANE Select	c.1315G>A	p.Gly439Ser	missense	Exon 9 of 14	ENSP00000331736.7	P16581
	SELE	ENST00000367776.5	TSL:5	c.1126G>A	p.Gly376Ser	missense	Exon 7 of 12	ENSP00000356750.1	Q5TI73
	SELE	ENST00000367775.5	TSL:5	c.940G>A	p.Gly314Ser	missense	Exon 6 of 11	ENSP00000356749.1	Q5TI75

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461772 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 727184

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86230

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111954

Other (OTH) AF: 0.0000166 AC: 1 AN: 60390

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.039	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.15	T
Eigen	Uncertain	0.37
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.017	T
MetaRNN	Pathogenic	0.90	D
MetaSVM	Uncertain	-0.057	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		2.7
PrimateAI	Benign	0.35	T
PROVEAN	Pathogenic	-4.7	D
REVEL	Uncertain	0.38
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.051	T
Polyphen		0.99	D
Vest4		0.30
MutPred		0.89		Gain of disorder (P = 0.0621)
MVP		0.84
MPC		0.27
ClinPred		0.81	D
GERP RS		5.0
gMVP		0.75
Mutation Taster		=78/22	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr1-169697033;