17-64356203-C-T

Position:

• chr17-64356203-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_000442.5(PECAM1):​c.1688G>A​(p.Ser563Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.443 in 474,152 control chromosomes in the GnomAD database, including 50,015 homozygotes. In-silico tool predicts a benign outcome for this variant. 5/7 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S563I) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.38 (12830 hom., cov: 28)
  • Exomes 𝑓: 0.47 (37185 hom.)
• Consequence: PECAM1 NM_000442.5 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• 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 Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.003622979).
• BP6: Variant 17-64356203-C-T is Benign according to our data. Variant chr17-64356203-C-T is described in ClinVar as [Benign]. Clinvar id is 812624.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.513 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PECAM1	NM_000442.5	c.1688G>A	p.Ser563Asn	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>A	p.Ser563Asn	missense_variant	8/16	1	NM_000442.5	ENSP00000457421	P1

Frequencies

GnomAD3 genomes AF: 0.382 AC: 57631 AN: 150962 Hom.: 12837 Cov.: 28

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.323

Gnomad AMR AF: 0.386

Gnomad ASJ AF: 0.426

Gnomad EAS AF: 0.529

Gnomad SAS AF: 0.414

Gnomad FIN AF: 0.523

Gnomad MID AF: 0.293

Gnomad NFE AF: 0.492

Gnomad OTH AF: 0.367

GnomAD4 exome AF: 0.472 AC: 152449 AN: 323070 Hom.: 37185 Cov.: 0 AF XY: 0.474 AC XY: 79820 AN XY: 168558

Gnomad4 AFR exome AF: 0.138

Gnomad4 AMR exome AF: 0.383

Gnomad4 ASJ exome AF: 0.413

Gnomad4 EAS exome AF: 0.488

Gnomad4 SAS exome AF: 0.413

Gnomad4 FIN exome AF: 0.522

Gnomad4 NFE exome AF: 0.493

Gnomad4 OTH exome AF: 0.445

GnomAD4 genome AF: 0.381 AC: 57625 AN: 151082 Hom.: 12830 Cov.: 28 AF XY: 0.383 AC XY: 28217 AN XY: 73724

Gnomad4 AFR AF: 0.140

Gnomad4 AMR AF: 0.386

Gnomad4 ASJ AF: 0.426

Gnomad4 EAS AF: 0.529

Gnomad4 SAS AF: 0.414

Gnomad4 FIN AF: 0.523

Gnomad4 NFE AF: 0.492

Gnomad4 OTH AF: 0.364

Alfa AF: 0.401 Hom.: 1760

Bravo AF: 0.356

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

Three Vessel Coronary Disease Benign:1

Benign, no assertion criteria provided

clinical testing

Department of Cardiology, Chinese Academy of Medical Sciences, Fuwai Hospital

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
CADD	Benign	18
DEOGEN2	Benign	0.031	T
LIST_S2	Benign	0.52	T
MetaRNN	Benign	0.0036	T
PROVEAN	Benign	-1.6	N
Sift	Benign	0.058	T
Sift4G	Uncertain	0.046	D
Vest4		0.23
gMVP		0.34

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: -;