rs12953

Positions:

• chr17-64356203-C-A
• chr17-64356203-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.

• 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	Protein	UniProt
PECAM1	NM_000442.5	c.1688G>T	p.Ser563Ile	missense_variant	8/16	ENST00000563924.6	NP_000433.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PECAM1	ENST00000563924.6	c.1688G>T	p.Ser563Ile	missense_variant	8/16	1	NM_000442.5	ENSP00000457421	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: -;