dbSNP rs668: PECAM1:p.Val125Met (chr17-64377836-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000442.5(PECAM1):c.373G>A(p.Val125Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000659 in 151,776 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. V125L) has been classified as Benign.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 30)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PECAM1
NM_000442.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.159

Publications

71 publications found

Variant links:

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]

PECAM1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.115790725).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000442.5. 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
	PECAM1	NM_000442.5	MANE Select	c.373G>A	p.Val125Met	missense	Exon 3 of 16	NP_000433.4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PECAM1	ENST00000563924.6	TSL:1 MANE Select	c.373G>A	p.Val125Met	missense	Exon 3 of 16	ENSP00000457421.1	P16284-1
PECAM1	ENST00000904885.1		c.373G>A	p.Val125Met	missense	Exon 3 of 17	ENSP00000574944.1
PECAM1	ENST00000904891.1		c.373G>A	p.Val125Met	missense	Exon 3 of 17	ENSP00000574950.1

Frequencies

GnomAD3 genomes

AF:

0.00000659

AC:

AN:

151776

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

323080

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

168572

African (AFR)

AF:

0.00

AC:

AN:

9066

American (AMR)

AF:

0.00

AC:

AN:

16458

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

10194

East Asian (EAS)

AF:

0.00

AC:

AN:

26862

South Asian (SAS)

AF:

0.00

AC:

AN:

10054

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39178

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1366

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

191068

Other (OTH)

AF:

0.00

AC:

AN:

18834

GnomAD4 genome

AF:

0.00000659

AC:

AN:

151776

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74090

show subpopulations

African (AFR)

AF:

0.0000242

AC:

AN:

41260

American (AMR)

AF:

0.00

AC:

AN:

15232

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5164

South Asian (SAS)

AF:

0.00

AC:

AN:

4812

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10548

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67980

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

245

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.36

CADD

Benign

(source)

LIST_S2

Uncertain

0.89

MetaRNN

Benign

0.12

PhyloP100

-0.16

PROVEAN

Benign

-0.85

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.0090

Vest4

0.34

gMVP

0.36

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over