rs12953

chr17-64356203-C-Achr17-64356203-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_000442.5(PECAM1):c.1688G>T(p.Ser563Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S563N) has been classified as Benign.

• Frequency: Genomes: not found (cov: 28)
• Consequence: PECAM1 NM_000442.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.10

Genes affected

PECAM1 (HGNC:8823): (platelet and endothelial cell adhesion molecule 1) The protein encoded by this gene is found on the surface of platelets, monocytes, neutrophils, and some types of T-cells, and makes up a large portion of endothelial cell intercellular junctions. The encoded protein is a member of the immunoglobulin superfamily and is likely involved in leukocyte migration, angiogenesis, and integrin activation. [provided by RefSeq, May 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29889402).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PECAM1	NM_000442.5	c.1688G>T	p.Ser563Ile	missense_variant	8/16	ENST00000563924.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PECAM1	ENST00000563924.6	c.1688G>T	p.Ser563Ile	missense_variant	8/16	1	NM_000442.5	P1

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 28

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
Cadd	Uncertain	23
DEOGEN2	Benign	0.11	T
LIST_S2	Benign	0.74	T
MetaRNN	Benign	0.30	T
PROVEAN	Uncertain	-4.2	D
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0070	D
Vest4		0.32
gMVP		0.58

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12953; hg19: -;